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  1. Article ; Online: Clinical electrophysiology of the optic nerve and retinal ganglion cells.

    Marmoy, Oliver R / Viswanathan, Suresh

    Eye (London, England)

    2021  Volume 35, Issue 9, Page(s) 2386–2405

    Abstract: 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 ...

    Abstract 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. In this review, 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, compressive, toxic/nutritional, traumatic, vascular, inflammatory and intracranial causes for optic nerve or retinal ganglion cell dysfunction. The benefits of objective, electrophysiological measurement of the retinal ganglion cells and optic nerve are discussed, as are their applications in clinical diagnosis of disease, determining prognosis, monitoring progression and response to novel therapies.
    MeSH term(s) Electroretinography ; Evoked Potentials, Visual ; Glaucoma/diagnosis ; Humans ; Optic Nerve ; Retinal Ganglion Cells
    Language English
    Publishing date 2021-06-11
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 91001-6
    ISSN 1476-5454 ; 0950-222X
    ISSN (online) 1476-5454
    ISSN 0950-222X
    DOI 10.1038/s41433-021-01614-x
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  2. Article ; Online: Correction: Clinical electrophysiology of the optic nerve and retinal ganglion cells.

    Marmoy, Oliver R / Viswanathan, Suresh

    Eye (London, England)

    2021  Volume 37, Issue 6, Page(s) 1290

    Language English
    Publishing date 2021-10-15
    Publishing country England
    Document type Published Erratum
    ZDB-ID 91001-6
    ISSN 1476-5454 ; 0950-222X
    ISSN (online) 1476-5454
    ISSN 0950-222X
    DOI 10.1038/s41433-021-01798-2
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  3. Article ; Online: Contrast Sensitivity of ON and OFF Human Retinal Pathways in Myopia.

    Poudel, Sabina / Jin, Jianzhong / Rahimi-Nasrabadi, Hamed / Dellostritto, Stephen / Dul, Mitchell W / Viswanathan, Suresh / Alonso, Jose-Manuel

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2024  Volume 44, Issue 3

    Abstract: The human visual cortex processes light and dark stimuli with ON and OFF pathways that are differently modulated by luminance contrast. We have previously demonstrated that ON cortical pathways have higher contrast sensitivity than OFF cortical pathways ... ...

    Abstract The human visual cortex processes light and dark stimuli with ON and OFF pathways that are differently modulated by luminance contrast. We have previously demonstrated that ON cortical pathways have higher contrast sensitivity than OFF cortical pathways and the difference increases with luminance range (defined as the maximum minus minimum luminance in the scene). Here, we demonstrate that these ON-OFF cortical differences are already present in the human retina and that retinal responses measured with electroretinography are more affected by reductions in luminance range than cortical responses measured with electroencephalography. Moreover, we show that ON-OFF pathway differences measured with electroretinography become more pronounced in myopia, a visual disorder that elongates the eye and blurs vision at far distance. We find that, as the eye axial length increases across subjects, ON retinal pathways become less responsive, slower in response latency, less sensitive, and less effective and slower at driving pupil constriction. Based on these results, we conclude that myopia is associated with a deficit in ON pathway function that decreases the ability of the retina to process low contrast and regulate retinal illuminance in bright environments.
    MeSH term(s) Humans ; Contrast Sensitivity ; Retina/physiology ; Myopia ; Vision, Ocular ; Electroretinography ; Photic Stimulation
    Language English
    Publishing date 2024-01-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.1487-23.2023
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  4. Article ; Online: Impact of traumatic brain injury on vision.

    Viswanathan, Suresh / Port, Nicholas / Master, Christina L / Pardue, Machelle T

    Vision research

    2022  Volume 204, Page(s) 108176

    MeSH term(s) Humans ; Brain Injuries, Traumatic ; Vision, Ocular ; Vision Disorders/etiology
    Language English
    Publishing date 2022-12-23
    Publishing country England
    Document type Editorial
    ZDB-ID 200427-6
    ISSN 1878-5646 ; 0042-6989
    ISSN (online) 1878-5646
    ISSN 0042-6989
    DOI 10.1016/j.visres.2022.108176
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  5. Article: A clinically viable approach to restoring visual function using optogenetic gene therapy.

    Yan, Boyuan / Viswanathan, Suresh / Brodie, Scott E / Deng, Wen-Tao / Coleman, Kirsten E / Hauswirth, William W / Nirenberg, Sheila

    Molecular therapy. Methods & clinical development

    2023  Volume 29, Page(s) 406–417

    Abstract: Optogenetic gene therapies offer a promising strategy for restoring vision to patients with retinal degenerative diseases, such as retinitis pigmentosa (RP). Several clinical trials have begun in this area using different vectors and optogenetic proteins ...

    Abstract Optogenetic gene therapies offer a promising strategy for restoring vision to patients with retinal degenerative diseases, such as retinitis pigmentosa (RP). Several clinical trials have begun in this area using different vectors and optogenetic proteins (Clinical Identifiers: NCT02556736, NCT03326336, NCT04945772, and NCT04278131). Here we present preclinical efficacy and safety data for the NCT04278131 trial, which uses an AAV2 vector and Chronos as the optogenetic protein. Efficacy was assessed in mice in a dose-dependent manner using electroretinograms (ERGs). Safety was assessed in rats, nonhuman primates, and mice, using several tests, including immunohistochemical analyses and cell counts (rats), electroretinograms (nonhuman primates), and ocular toxicology assays (mice). The results showed that Chronos-expressing vectors were efficacious over a broad range of vector doses and stimulating light intensities, and were well tolerated: no test article-related findings were observed in the anatomical and electrophysiological assays performed.
    Language English
    Publishing date 2023-05-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2023.05.005
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  6. Article ; Online: Neuroprotection of the Inner Retina Also Prevents Secondary Outer Retinal Pathology in a Mouse Model of Glaucoma.

    Kumar, Sandeep / Ramakrishnan, Hariharasubramanian / Viswanathan, Suresh / Akopian, Abram / Bloomfield, Stewart A

    Investigative ophthalmology & visual science

    2021  Volume 62, Issue 9, Page(s) 35

    Abstract: Purpose: We examined structural and functional changes in the outer retina of a mouse model of glaucoma. We examined whether these changes are a secondary consequence of damage in the inner retina and whether neuroprotection of the inner retina also ... ...

    Abstract Purpose: We examined structural and functional changes in the outer retina of a mouse model of glaucoma. We examined whether these changes are a secondary consequence of damage in the inner retina and whether neuroprotection of the inner retina also prevents outer retinal changes.
    Methods: We used an established microbead occlusion model of glaucoma whereby intraocular pressure (IOP) was elevated. Specific antibodies were used to label rod and cone bipolar cells (BCs), horizontal cells (HCs), and retinal ganglion cells (RGCs), as well as synaptic components in control and glaucomatous eyes, to assess structural damage and cell loss. ERG recordings were made to assess outer retina function.
    Results: We found structural and functional damage of BCs, including significant cell loss and dendritic/axonal remodeling of HCs, following IOP elevation. The first significant loss of both BCs occurred at 4 to 5 weeks after microbead injection. However, early changes in the dendritic structure of RGCs were observed at 3 weeks, but significant changes in the rod BC axon terminal structure were not seen until 4 weeks. We found that protection of inner retinal neurons in glaucomatous eyes by pharmacological blockade of gap junctions or genetic ablation of connexin 36 largely prevented outer retinal damage.
    Conclusions: Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.
    MeSH term(s) Animals ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Disease Models, Animal ; Electroretinography ; Glaucoma/pathology ; Glaucoma/physiopathology ; Glaucoma/prevention & control ; Immunohistochemistry ; Injections ; Intraocular Pressure/physiology ; Meclofenamic Acid/administration & dosage ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron ; Neuroprotection/physiology ; Retinal Photoreceptor Cell Inner Segment/drug effects ; Retinal Photoreceptor Cell Inner Segment/metabolism ; Retinal Photoreceptor Cell Inner Segment/ultrastructure ; Mice
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal ; Meclofenamic Acid (48I5LU4ZWD)
    Language English
    Publishing date 2021-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 391794-0
    ISSN 1552-5783 ; 0146-0404
    ISSN (online) 1552-5783
    ISSN 0146-0404
    DOI 10.1167/iovs.62.9.35
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  7. Article ; Online: A Robust Microbead Occlusion Model of Glaucoma for the Common Marmoset.

    Kumar, Sandeep / Benavente-Perez, Alexandra / Ablordeppey, Reynolds / Lin, Carol / Viswanathan, Suresh / Akopian, Abram / Bloomfield, Stewart A

    Translational vision science & technology

    2022  Volume 11, Issue 1, Page(s) 14

    Abstract: Purpose: To establish a robust experimental model of glaucoma in the common marmoset (Callithrix jacchus), a New World primate, using an intracameral microbead injection technique.: Methods: Elevated intraocular pressure (IOP) was induced by an ... ...

    Abstract Purpose: To establish a robust experimental model of glaucoma in the common marmoset (Callithrix jacchus), a New World primate, using an intracameral microbead injection technique.
    Methods: Elevated intraocular pressure (IOP) was induced by an injection of polystyrene microbeads. Morphologic changes in the retina and optic nerve of glaucomatous eyes were assessed and electroretinogram (ERG) recordings were performed to evaluate functional changes.
    Results: Microbead injections induced a sustained IOP elevation for at least 10 weeks in a reproducible manner. At the end of the 10-week experimental period, there was significant loss of retinal ganglion cells (RGCs) in all quadrants and eccentricities, although it was more prominent in the mid-peripheral and peripheral regions. This was consistent with a thinning of the Retinal nerve fiber layer (RNFL) seen in spectral domain optical coherence tomography scans. Surviving RGCs showed marked changes in morphology, including somatic shrinkage and dendritic atrophy. Retinas also showed significant gliosis. The amplitude of the ERG photopic negative response, with subsequent a- and b-wave changes, was reduced in glaucomatous eyes. The optic nerve of glaucomatous eyes showed expanded cupping, disorganization of the astrocytic matrix, axonal loss, and gliosis.
    Conclusions: We developed a robust and reproducible model of glaucoma in the marmoset. The model exhibits both structural and functional alterations of retina and optic nerve characteristic of glaucoma in humans and animal models.
    Translational relevance: The glaucoma model in the marmoset described here forms a robust method to study the disease etiology, progression, and potential therapies in a nonhuman primate, allowing for more effective translation of animal data to humans.
    MeSH term(s) Animals ; Callithrix ; Glaucoma ; Intraocular Pressure ; Microspheres ; Retinal Ganglion Cells
    Language English
    Publishing date 2022-01-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2674602-5
    ISSN 2164-2591 ; 2164-2591
    ISSN (online) 2164-2591
    ISSN 2164-2591
    DOI 10.1167/tvst.11.1.14
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  8. Article ; Online: Test-retest reliability of the multifocal photopic negative response.

    Van Alstine, Anthony W / Viswanathan, Suresh

    Documenta ophthalmologica. Advances in ophthalmology

    2017  Volume 134, Issue 1, Page(s) 25–36

    Abstract: Purpose: To assess the test-retest reliability of the multifocal photopic negative response (mfPhNR) of normal human subjects.: Methods: Multifocal electroretinograms were recorded from one eye of 61 healthy adult subjects on two separate days using ... ...

    Abstract Purpose: To assess the test-retest reliability of the multifocal photopic negative response (mfPhNR) of normal human subjects.
    Methods: Multifocal electroretinograms were recorded from one eye of 61 healthy adult subjects on two separate days using a Visual Evoked Response Imaging System software version 4.3 (EDI, San Mateo, California). The visual stimulus delivered on a 75-Hz monitor consisted of seven equal-sized hexagons each subtending 12° of visual angle. The m-step exponent was 9, and the m-sequence was slowed to include at least 30 blank frames after each flash. Only the first slice of the first-order kernel was analyzed. The mfPhNR amplitude was measured at a fixed time in the trough from baseline (BT) as well as at the same fixed time in the trough from the preceding b-wave peak (PT). Additionally, we also analyzed BT normalized either to PT (BT/PT) or to the b-wave amplitude (BT/b-wave). The relative reliability of test-retest differences for each test location was estimated by the Wilcoxon matched-pair signed-rank test and intraclass correlation coefficients (ICC). Absolute test-retest reliability was estimated by Bland-Altman analysis.
    Results: The test-retest amplitude differences for neither of the two measurement techniques were statistically significant as determined by Wilcoxon matched-pair signed-rank test. PT measurements showed greater ICC values than BT amplitude measurements for all test locations. For each measurement technique, the ICC value of the macular response was greater than that of the surrounding locations. The mean test-retest difference was close to zero for both techniques at each of the test locations, and while the coefficient of reliability (COR-1.96 times the standard deviation of the test-retest difference) was comparable for the two techniques at each test location when expressed in nanovolts, the %COR (COR normalized to the mean test and retest amplitudes) was superior for PT than BT measurements. The ICC and COR were comparable for the BT/PT and BT/b-wave ratios and were better than the ICC and COR for BT but worse than PT.
    Conclusion: mfPhNR amplitude measured at a fixed time in the trough from the preceding b-wave peak (PT) shows greater test-retest reliability when compared to amplitude measurement from baseline (BT) or BT amplitude normalized to either the PT or b-wave amplitudes.
    MeSH term(s) Adult ; Aged ; Electroretinography/methods ; Electroretinography/standards ; Evoked Potentials, Visual/physiology ; Female ; Humans ; Male ; Middle Aged ; Reproducibility of Results ; Retina/physiology ; Vision, Ocular/physiology ; Young Adult
    Language English
    Publishing date 2017-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 212594-8
    ISSN 1573-2622 ; 0012-4486
    ISSN (online) 1573-2622
    ISSN 0012-4486
    DOI 10.1007/s10633-016-9569-3
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  9. Article ; Online: Intensity response function of the photopic negative response (PhNR): effect of age and test-retest reliability.

    Joshi, Nabin R / Ly, Emma / Viswanathan, Suresh

    Documenta ophthalmologica. Advances in ophthalmology

    2017  Volume 135, Issue 1, Page(s) 1–16

    Abstract: Purpose: To assess the effect of age and test-retest reliability of the intensity response function of the full-field photopic negative response (PhNR) in normal healthy human subjects.: Methods: Full-field electroretinograms (ERGs) were recorded ... ...

    Abstract Purpose: To assess the effect of age and test-retest reliability of the intensity response function of the full-field photopic negative response (PhNR) in normal healthy human subjects.
    Methods: Full-field electroretinograms (ERGs) were recorded from one eye of 45 subjects, and 39 of these subjects were tested on two separate days with a Diagnosys Espion System (Lowell, MA, USA). The visual stimuli consisted of brief (<5 ms) red flashes ranging from 0.00625 to 6.4 phot cd.s/m
    Results: V
    Conclusion: V
    MeSH term(s) Adult ; Aged ; Color Vision/physiology ; Electroretinography ; Female ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Photic Stimulation ; Reproducibility of Results ; Retina/physiology ; Retinal Ganglion Cells/physiology ; Young Adult
    Language English
    Publishing date 2017-05-15
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 212594-8
    ISSN 1573-2622 ; 0012-4486
    ISSN (online) 1573-2622
    ISSN 0012-4486
    DOI 10.1007/s10633-017-9591-0
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  10. Article ; Online: ISCEV standard for clinical multifocal electroretinography (mfERG) (2021 update).

    Hoffmann, Michael B / Bach, Michael / Kondo, Mineo / Li, Shiying / Walker, Sinead / Holopigian, Karen / Viswanathan, Suresh / Robson, Anthony G

    Documenta ophthalmologica. Advances in ophthalmology

    2021  Volume 142, Issue 1, Page(s) 5–16

    Abstract: The multifocal electroretinogram (mfERG) is an electrophysiological test that allows the function of multiple discrete areas of the retina to be tested simultaneously. This document, from the International Society for Clinical Electrophysiology of Vision ...

    Abstract The multifocal electroretinogram (mfERG) is an electrophysiological test that allows the function of multiple discrete areas of the retina to be tested simultaneously. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV standard for clinical mfERG and defines minimum protocols for basic clinical mfERG recording and reporting so that responses can be recognized and compared from different laboratories worldwide. The major changes compared with the previous mfERG standard relate to the minimum length of m-sequences used for recording, reporting of results and a change in document format, to be more consistent with other ISCEV standards.
    MeSH term(s) Electroretinography ; Retina/diagnostic imaging ; Vision, Ocular
    Language English
    Publishing date 2021-01-25
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 212594-8
    ISSN 1573-2622 ; 0012-4486
    ISSN (online) 1573-2622
    ISSN 0012-4486
    DOI 10.1007/s10633-020-09812-w
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