Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity

Jacque L. Duncan; Wendi Liang; Maureen G. Maguire; Isabelle Audo; Allison R. Ayala; David G. Birch; Joseph Carroll; Janet K. Cheetham; Simona Degli Esposti; Todd A. Durham; Laura Erker; Sina Farsiu; Frederick L. Ferris; Elise Heon; Robert B. Hufnagel; Alessandro Iannaccone; Glenn J. Jaffe; Christine N. Kay; Michel Michaelides; Mark E. Pennesi; José Alain Sahel

doi:10.1016/j.ajo.2020.05.024

Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity

Jacque L. Duncan, Wendi Liang, Maureen G. Maguire, Isabelle Audo, Allison R. Ayala, David G. Birch, Joseph Carroll, Janet K. Cheetham, Simona Degli Esposti, Todd A. Durham, Laura Erker, Sina Farsiu, Frederick L. Ferris, Elise Heon, Robert B. Hufnagel, Alessandro Iannaccone, Glenn J. Jaffe, Christine N. Kay, Michel Michaelides, Mark E. PennesiJosé Alain Sahel

Ophthalmology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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

Original language	English (US)
Pages (from-to)	87-100
Number of pages	14
Journal	American journal of ophthalmology
Volume	219
DOIs	https://doi.org/10.1016/j.ajo.2020.05.024
State	Published - Nov 2020

ASJC Scopus subject areas

Ophthalmology

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10.1016/j.ajo.2020.05.024

Cite this

Duncan, J. L., Liang, W., Maguire, M. G., Audo, I., Ayala, A. R., Birch, D. G., Carroll, J., Cheetham, J. K., Esposti, S. D., Durham, T. A., Erker, L., Farsiu, S., Ferris, F. L., Heon, E., Hufnagel, R. B., Iannaccone, A., Jaffe, G. J., Kay, C. N., Michaelides, M., ... Sahel, J. A. (2020). Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity. American journal of ophthalmology, 219, 87-100. https://doi.org/10.1016/j.ajo.2020.05.024

Duncan, JL, Liang, W, Maguire, MG, Audo, I, Ayala, AR, Birch, DG, Carroll, J, Cheetham, JK, Esposti, SD, Durham, TA, Erker, L, Farsiu, S, Ferris, FL, Heon, E, Hufnagel, RB, Iannaccone, A, Jaffe, GJ, Kay, CN, Michaelides, M, Pennesi, ME & Sahel, JA 2020, 'Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity', American journal of ophthalmology, vol. 219, pp. 87-100. https://doi.org/10.1016/j.ajo.2020.05.024

@article{d646de84022c4543b1248f893a576307,

title = "Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity",

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

author = "Duncan, {Jacque L.} and Wendi Liang and Maguire, {Maureen G.} and Isabelle Audo and Ayala, {Allison R.} and Birch, {David G.} and Joseph Carroll and Cheetham, {Janet K.} and Esposti, {Simona Degli} and Durham, {Todd A.} and Laura Erker and Sina Farsiu and Ferris, {Frederick L.} and Elise Heon and Hufnagel, {Robert B.} and Alessandro Iannaccone and Jaffe, {Glenn J.} and Kay, {Christine N.} and Michel Michaelides and Pennesi, {Mark E.} and Sahel, {Jos{\'e} Alain}",

note = "Funding Information: Funding/Support: This work was supported by funds from the Foundation Fighting Blindness, Columbia, MD, USA. Financial Disclosures: J. Cheetham reports personal fees from Foundation Fighting Blindness, Columbia, MD, and personal fees from Allergan, Dublin IR. L. Erker reports grants from the NIH, Bethesda, MD; FDA Orphan, Silver Spring, MD; Department of Defense Grant, VA; and Wynn Gund grant, from Foundation Fighting Blindness during the conduct of the study; other relevant conflict of interest from Sanofi, Paris, France; Applied Genetic Technologies Corporation, Alachua, FL; Meira Gtx, New York, NY, NightstaRx, London, UK; and Novelion, Vancouver, BC, Canada. S. Degli Esposti reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and receives personal fees from GSK, UK; Novartis, UK; Bayer, UK; and Allergan, UK, outside the submitted work. M. Maguire reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research. J. Duncan reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; personal fees from 4D Therapeutics, Emeryville, CA; Applied Genetic Technologies Corporation, Alachua, FL; Editas Medicine, Inc, Cambridge, MA; Biogen/NightstaRx Therapeutics, London, UK; ProQR Therapeutics, Leiden, Netherlands; Spark Therapeutics, Philadelphia, PA; SparingVision, Paris, France; Vedere Bio, Cambridge, MA; Horama, Paris, France; grants from Foundation Fighting Blindness, Columbia, MD; Research to Prevent Blindness, New York, NY; National Eye Institute, Bethesda, MD; and personal fees from Miller Medical Communications, New York, NY, outside the submitted work. A. Iannaccone reports grants and personal fees from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study; personal fees from Alia Therapeutics, Trento, Italy; ClearViewHealthcare Partners, Newton, MA; Teladoc Health, Westwood, MA; GLG Group, San Francisco, CA; Guidepoint, Boston, MA; Astellas Institute for Regenerative Medicine, Marlborough, MA; Roivant Pharma, New York, NY; Editas Medicine, Cambridge, MA; Rhythm Pharmaceuticals, Boston, MA; IQVIA, Durham, NC; Gyroscope, Stevenage, UK; and Ocugen, Malvern, PA; grants from AGTC, Alachua, FL; Allergan, Dublin, Ireland; Acucela, Seattle, WA; ProQR, Leiden, Netherlands; Retinagenix, Seattle, WA; and 4D Molecular Therapeutics, Emeryville, CA outside the submitted work. D. Birch reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, and grant EY009076 from NIH, Bethesda, MD, during the conduct of the study; personal fees from ProQR, Leiden, Netherlands; Nacuity, Fort Worth, TX; AGTC, Alachua, FL; and Editas, Cambridge, MA, outside the submitted work. S. Farsiu reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; grants from Foundation Fighting Blindness, Columbia, MD, outside the submitted work; and Duke University, Durham, NC; he has developed DOCTRAP software, a version of which is used for this study. This software is also used in other studies that are sponsored by external entities that pay Duke in form of research grants or contracts. Part of his compensation and research funds comes from such activities. J. Sahel reports grants from LabEx LIFESENSES (ANR-10-LABX-65), Paris, France; and grants from IHU FOReSIGHT (ANR-18-IAHU-01), Paris, France, during the conduct of the study. J. Carroll reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and personal fees from MeiraGTx outside the submitted work. M. Pennesi reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; consulting fees from Allergan/Editas, Cambridge, MA; Spark Therapeutics, Philadelphia, PA; Wave Biosciences, Cambridge, MA; Astellas Pharmaceuticals, Chuo City, Tokyo, Japan; RegenexBio, Rockville, MD; and Iveric, New York, NY; other from Biogen, Cambridge, MA; Novartis, Basel, Switzerland; Adverum, Redwood City, CA; Gensight, Paris, France; ProQR, Leiden, Netherlands; Horama, Paris, France; Eyevensys, Paris, France; Nayan, Seattle, WA; SparingVision, Paris, France; AGTC, Alachua, FL; and Sanofi, Paris, France outside the submitted work; personal fees and other from Nacuity, Fort Worth, TX; Ocugen, Malvern, PA; and Vedere Bio, Cambridge, MA. M. Michaelides reports personal fees from MeiraGTx, Stargazer Pharma, Acucela, Astellas, ProQR, and 2CTech, outside the submitted work; and Stock options with MeiraGTx, New York, NY. G. Jaffe reports other from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research; other from Novartis, Basel, Switzerland during the conduct of the study. I. Audo reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study. C. Kay reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study A. Ayala, T. Durham, R. Hufnagel, F. Ferris, E. Heon, and W. Liang have no financial disclosures. Funding Information: All authors attest that they meet the current ICMJE criteria for authorship. Foundation Fighting Blindness (FFB) Consortium: David Birch is supported by NIH grant EY009076. Isabelle Audo is a member of the French National Rare Diseases network of the eye and the ear, SENSGENE, and the ERN-EYE (European Reference Network for Rare Eye Diseases) and is supported by RHU-Light4deaf [ANR-15-RHU-0001] and IHU FOReSIGHT [ANR-18-IAHU-0001] supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program . Jacque Duncan is supported by Research to Prevent Blindness (UCSF). Alessandro Iannaccone is supported by an unrestricted departmental grant to the Duke Eye Center from Research to Prevent Blindness, New York, NY. Michel Michaelides is supported by a grant from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology. Mark Pennesi is supported by an unrestricted grant from RPB to Casey Eye Institute and a core grant NIH P30EY010572. Funding Information: Funding/Support: This work was supported by funds from the Foundation Fighting Blindness, Columbia, MD, USA. Financial Disclosures: J. Cheetham reports personal fees from Foundation Fighting Blindness, Columbia, MD, and personal fees from Allergan, Dublin IR. L. Erker reports grants from the NIH, Bethesda, MD; FDA Orphan, Silver Spring, MD; Department of Defense Grant, VA; and Wynn Gund grant, from Foundation Fighting Blindness during the conduct of the study; other relevant conflict of interest from Sanofi, Paris, France; Applied Genetic Technologies Corporation, Alachua, FL; Meira Gtx, New York, NY, NightstaRx, London, UK; and Novelion, Vancouver, BC, Canada. S. Degli Esposti reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and receives personal fees from GSK, UK; Novartis, UK; Bayer, UK; and Allergan, UK, outside the submitted work. M. Maguire reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research. J. Duncan reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; personal fees from 4D Therapeutics, Emeryville, CA; Applied Genetic Technologies Corporation, Alachua, FL; Editas Medicine, Inc, Cambridge, MA; Biogen/NightstaRx Therapeutics, London, UK; ProQR Therapeutics, Leiden, Netherlands; Spark Therapeutics, Philadelphia, PA; SparingVision, Paris, France; Vedere Bio, Cambridge, MA; Horama, Paris, France; grants from Foundation Fighting Blindness, Columbia, MD; Research to Prevent Blindness, New York, NY; National Eye Institute, Bethesda, MD; and personal fees from Miller Medical Communications, New York, NY, outside the submitted work. A. Iannaccone reports grants and personal fees from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study; personal fees from Alia Therapeutics, Trento, Italy; ClearViewHealthcare Partners, Newton, MA; Teladoc Health, Westwood, MA; GLG Group, San Francisco, CA; Guidepoint, Boston, MA; Astellas Institute for Regenerative Medicine, Marlborough, MA; Roivant Pharma, New York, NY; Editas Medicine, Cambridge, MA; Rhythm Pharmaceuticals, Boston, MA; IQVIA, Durham, NC; Gyroscope, Stevenage, UK; and Ocugen, Malvern, PA; grants from AGTC, Alachua, FL; Allergan, Dublin, Ireland; Acucela, Seattle, WA; ProQR, Leiden, Netherlands; Retinagenix, Seattle, WA; and 4D Molecular Therapeutics, Emeryville, CA outside the submitted work. D. Birch reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, and grant EY009076 from NIH, Bethesda, MD, during the conduct of the study; personal fees from ProQR, Leiden, Netherlands; Nacuity, Fort Worth, TX; AGTC, Alachua, FL; and Editas, Cambridge, MA, outside the submitted work. S. Farsiu reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; grants from Foundation Fighting Blindness, Columbia, MD, outside the submitted work; and Duke University, Durham, NC; he has developed DOCTRAP software, a version of which is used for this study. This software is also used in other studies that are sponsored by external entities that pay Duke in form of research grants or contracts. Part of his compensation and research funds comes from such activities. J. Sahel reports grants from LabEx LIFESENSES (ANR-10-LABX-65), Paris, France; and grants from IHU FOReSIGHT (ANR-18-IAHU-01), Paris, France, during the conduct of the study. J. Carroll reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and personal fees from MeiraGTx outside the submitted work. M. Pennesi reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; consulting fees from Allergan/Editas, Cambridge, MA; Spark Therapeutics, Philadelphia, PA; Wave Biosciences, Cambridge, MA; Astellas Pharmaceuticals, Chuo City, Tokyo, Japan; RegenexBio, Rockville, MD; and Iveric, New York, NY; other from Biogen, Cambridge, MA; Novartis, Basel, Switzerland; Adverum, Redwood City, CA; Gensight, Paris, France; ProQR, Leiden, Netherlands; Horama, Paris, France; Eyevensys, Paris, France; Nayan, Seattle, WA; SparingVision, Paris, France; AGTC, Alachua, FL; and Sanofi, Paris, France outside the submitted work; personal fees and other from Nacuity, Fort Worth, TX; Ocugen, Malvern, PA; and Vedere Bio, Cambridge, MA. M. Michaelides reports personal fees from MeiraGTx, Stargazer Pharma, Acucela, Astellas, ProQR, and 2CTech, outside the submitted work; and Stock options with MeiraGTx, New York, NY. G. Jaffe reports other from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research; other from Novartis, Basel, Switzerland during the conduct of the study. I. Audo reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study. C. Kay reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study A. Ayala, T. Durham, R. Hufnagel, F. Ferris, E. Heon, and W. Liang have no financial disclosures. All authors attest that they meet the current ICMJE criteria for authorship. Foundation Fighting Blindness (FFB) Consortium: David Birch is supported by NIH grant EY009076. Isabelle Audo is a member of the French National Rare Diseases network of the eye and the ear, SENSGENE, and the ERN-EYE (European Reference Network for Rare Eye Diseases) and is supported by RHU-Light4deaf [ANR-15-RHU-0001] and IHU FOReSIGHT [ANR-18-IAHU-0001] supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program. Jacque Duncan is supported by Research to Prevent Blindness (UCSF). Alessandro Iannaccone is supported by an unrestricted departmental grant to the Duke Eye Center from Research to Prevent Blindness, New York, NY. Michel Michaelides is supported by a grant from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology. Mark Pennesi is supported by an unrestricted grant from RPB to Casey Eye Institute and a core grant NIH P30EY010572. Acknowledgments: Foundation Fighting Blindness (FFB) Consortium Contributors to the RUSH2A Protocol. FFB Consortium Clinical Sites: Clinical sites participating in this protocol are listed in order by number of participants enrolled into the study. The number of participants enrolled is noted in parentheses preceded by the site location and the site name. Personnel are listed as (I) for Study Investigator, (C) for Coordinator, and (T) for Technician. San Francisco, CA - UCSF Department of Ophthalmology (18): Jacque Duncan (I), Arshia Mian (C), Yiran Liu (C), Mary Lew (C, T), John Peterson (T), Tom Hernandez (T), Betty Hom (T), Hoover Chan (T). Portland, OR - Oregon Health & Science University (14): Mark Pennesi (I), Paul Yang (I), Annelise Haft (C,T), Jordan Barth (T), Chiedozie Ukachukwu (T), Gareth Harman (T), Jocelyn Hui (T), Jennifer Hilgeman (T), Virinda Boyle (T), Scott Pickell (T), Darius Liseckas (T). London, United Kingdom - Moorfields Eye Hospital (13): Michel Michaelides (I), Simona Delgi Esposti (I), Shweta Anand (I), William Tucker (I), Tabassum Master (C), Emma Treacy (C), Alexa King (C), Samiul Rahman (C), Tina Reetun (C), Emerson Tingco (C, T), Katherine Binstead (T), Sash Yoganand Jeetun (T), Nafaz Mohamed Illyias (T), Linda Burton (T), Selma Lewis (T), Graham Brown (T), Gareth Davey (T), Kanom Bibi (T), Vincent Rocco (T), Shabneez Laulloo (T), Tran Dang (T), Andrew Carter (T), Anne Georgiou (T), MinakoLisa Nathasingh (T). Nijmegen, Netherlands - Radboud University Medical Center (13): Carel Hoyng (I), Jack Weeda (C,T), Esmee Runhart (C), Hans Hermens (T). Paris, France - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DGOS CIC1423 (13): Jose-Alain Sahel (I), Saddek Mohand-Said (I), Isabelle Audo (I), Pierre Queromes (I), Celine Devisme (C), Charl?ne Da Silveira (C), Carole Romand (C), Serge Sancho (T), Sarah Baranes (T), Mathias Chapon (T), Juliette Amaudruz (T), C?line Chaumette (T), Aurore Girmens (T), Victoria Ganem (T). Dallas, TX - Retina Foundation of the Southwest (12): David Birch (I), Martin Klein (C, T), Kirsten Locke (C,T). Tubingen, Germany - Center for Ophthalmology/Clinic for Hereditary Retina Degenerations, University of T?bingen (11): Katarina Stingl (I), Laura Kuehlewein (I), Andrea Rindtorff (C,T), Benjamin-Phillip Beier (C,T), Gudrun H?rer (T), Michael Breuninger (T), Susanne Schweyer (T), Ulrike Fuchs (T), Susanne Kramer (T). Ann Arbor, MI - University of Michigan, Kellogg Eye Center (9): Thiran Jayasundera (I), Naheed W. Khan (I), Abigail Fahim (I), Kari Branham (I), Munira Hussain (C,T), Cailyn Wolford (C,T), Lindsay Godsey (C,T), Laura Trebesh (T), Kit Morehead (T). Boston, MA - Massachusetts Eye and Ear Infirmary (8): Rachel Huckfeldt (I), Tu Doan (C), Xiao-Hong Wen (C), John Hensel (T), Bethany Biron (T), Jasmeet Bhullar (T), Lisa Dennehy (T), Matthew DiRocco (T), Sarah Brett (T), Emorfily Potsidis (T), Yuji Che (T). Gainesville, FL - Vitreo Retinal Associates, P.A. (7): Christine Kay (I), Jing Zhang (C,T). Houston, TX - Baylor College of Medicine, Alkek Eye Center (7): John Timothy Stout (I), Tahira Scholle (I), Annika Joshi (C,T), Joseph Morales (T), Dana Barnett (T), Laine Maier (T). Durham, NC - Duke University Medical Center (6): Alessandro Iannaccone (I), Elmer Balajonda (C), Magaly Guerrero (C,T), Amy Clark (C,T), Victoria Griffiths (T), Ryan Imperio (T), Malina Sexton (T), Alexandra Bosquet (T), Marina Kedrov (T), Brian Lutman (T). Baltimore, MD - Johns Hopkins University Hospital, Wilmer Eye Institute (5): Mandeep Singh (I), Mary Frey (C,T), David Emmert (T), Mohamed Ahmed (T), Lisa Liberto (T), Jennifer Bassinger (T). Salt Lake City, UT - University of Utah, John Moran Eye Center (4): Paul Bernstein (I), Kara Halsey (C), Donnell Creel (T), Kelliann Farnsworth (T), Danielle Wiscombe (T), William Hubbard (T). Toronto, Canada - University of Toronto, Hospital for Sick Children (4): Elise Heon (I), Vaishnavi Batmanabane (C,T), Katelyn Macneill (T), Jeff Locke (T), Ajoy Vincent (I). Milwaukee, WI - The Medical College of Wisconsin Eye Institute (1): Thomas Connor, Jr (I), William Wirostko (I), Katie McKenney (C,T), Amber Roberts (T). FFB Consortium Coordinating Center: Jaeb Center for Health Research, Tampa, FL (staff as of 02/25/2020): Ken Arcieri, Allison Ayala, Elizabeth Caruana, Peiyao Cheng, Jennifer Kennedy, Nadine Label, Stephanie Lee, Wendi Liang, Olivia Parrillo, Rebecca Parsons, Elizabeth Smith. Casey Reading Center [CRC], Casey Eye Institute, Oregon Health Sciences University, Portland, OR (Electroretinography, Static Perimetry, and Kinetic Perimetry): Ellie Chegarnov, Laura Erker, Melissa Krahmer, Brandon Lujan, Audra Miller, Albert Romo, Edeleidys Sanchez Saucedo. Duke Reading Center [DRC], Duke University, Durham, NC (Optical Coherence Tomography and Microperimetry): Vivienne Fang, Sina Farsiu, Magaly Guerrero, Cynthia Heydary, Grace Huh, Glenn Jaffe, Leon Kwark, Eleonora Lad, Brittany Mullaney, Justin Myers, Jayne Nicholson, Katrina Winter. FFB Consortium Genetics Committee: Kari Branham, Stephen Daiger, Robert Hufnagel. FFB Consortium Executive Committee: Jacque Duncan (Chair), Allison Ayala, David Birch, Janet Cheetham, Todd Durham, Rick Ferris, Maureen Maguire, Mark Pennesi. FFB Consortium Audiology Reviewer: Carmen Brewer. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = nov,

doi = "10.1016/j.ajo.2020.05.024",

language = "English (US)",

volume = "219",

pages = "87--100",

journal = "American journal of ophthalmology",

issn = "0002-9394",

publisher = "Elsevier USA",

}

TY - JOUR

T1 - Baseline Visual Field Findings in the RUSH2A Study

T2 - Associated Factors and Correlation With Other Measures of Disease Severity

AU - Duncan, Jacque L.

AU - Liang, Wendi

AU - Maguire, Maureen G.

AU - Audo, Isabelle

AU - Ayala, Allison R.

AU - Birch, David G.

AU - Carroll, Joseph

AU - Cheetham, Janet K.

AU - Esposti, Simona Degli

AU - Durham, Todd A.

AU - Erker, Laura

AU - Farsiu, Sina

AU - Ferris, Frederick L.

AU - Heon, Elise

AU - Hufnagel, Robert B.

AU - Iannaccone, Alessandro

AU - Jaffe, Glenn J.

AU - Kay, Christine N.

AU - Michaelides, Michel

AU - Pennesi, Mark E.

AU - Sahel, José Alain

N1 - Funding Information: Funding/Support: This work was supported by funds from the Foundation Fighting Blindness, Columbia, MD, USA. Financial Disclosures: J. Cheetham reports personal fees from Foundation Fighting Blindness, Columbia, MD, and personal fees from Allergan, Dublin IR. L. Erker reports grants from the NIH, Bethesda, MD; FDA Orphan, Silver Spring, MD; Department of Defense Grant, VA; and Wynn Gund grant, from Foundation Fighting Blindness during the conduct of the study; other relevant conflict of interest from Sanofi, Paris, France; Applied Genetic Technologies Corporation, Alachua, FL; Meira Gtx, New York, NY, NightstaRx, London, UK; and Novelion, Vancouver, BC, Canada. S. Degli Esposti reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and receives personal fees from GSK, UK; Novartis, UK; Bayer, UK; and Allergan, UK, outside the submitted work. M. Maguire reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research. J. Duncan reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; personal fees from 4D Therapeutics, Emeryville, CA; Applied Genetic Technologies Corporation, Alachua, FL; Editas Medicine, Inc, Cambridge, MA; Biogen/NightstaRx Therapeutics, London, UK; ProQR Therapeutics, Leiden, Netherlands; Spark Therapeutics, Philadelphia, PA; SparingVision, Paris, France; Vedere Bio, Cambridge, MA; Horama, Paris, France; grants from Foundation Fighting Blindness, Columbia, MD; Research to Prevent Blindness, New York, NY; National Eye Institute, Bethesda, MD; and personal fees from Miller Medical Communications, New York, NY, outside the submitted work. A. Iannaccone reports grants and personal fees from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study; personal fees from Alia Therapeutics, Trento, Italy; ClearViewHealthcare Partners, Newton, MA; Teladoc Health, Westwood, MA; GLG Group, San Francisco, CA; Guidepoint, Boston, MA; Astellas Institute for Regenerative Medicine, Marlborough, MA; Roivant Pharma, New York, NY; Editas Medicine, Cambridge, MA; Rhythm Pharmaceuticals, Boston, MA; IQVIA, Durham, NC; Gyroscope, Stevenage, UK; and Ocugen, Malvern, PA; grants from AGTC, Alachua, FL; Allergan, Dublin, Ireland; Acucela, Seattle, WA; ProQR, Leiden, Netherlands; Retinagenix, Seattle, WA; and 4D Molecular Therapeutics, Emeryville, CA outside the submitted work. D. Birch reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, and grant EY009076 from NIH, Bethesda, MD, during the conduct of the study; personal fees from ProQR, Leiden, Netherlands; Nacuity, Fort Worth, TX; AGTC, Alachua, FL; and Editas, Cambridge, MA, outside the submitted work. S. Farsiu reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; grants from Foundation Fighting Blindness, Columbia, MD, outside the submitted work; and Duke University, Durham, NC; he has developed DOCTRAP software, a version of which is used for this study. This software is also used in other studies that are sponsored by external entities that pay Duke in form of research grants or contracts. Part of his compensation and research funds comes from such activities. J. Sahel reports grants from LabEx LIFESENSES (ANR-10-LABX-65), Paris, France; and grants from IHU FOReSIGHT (ANR-18-IAHU-01), Paris, France, during the conduct of the study. J. Carroll reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and personal fees from MeiraGTx outside the submitted work. M. Pennesi reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; consulting fees from Allergan/Editas, Cambridge, MA; Spark Therapeutics, Philadelphia, PA; Wave Biosciences, Cambridge, MA; Astellas Pharmaceuticals, Chuo City, Tokyo, Japan; RegenexBio, Rockville, MD; and Iveric, New York, NY; other from Biogen, Cambridge, MA; Novartis, Basel, Switzerland; Adverum, Redwood City, CA; Gensight, Paris, France; ProQR, Leiden, Netherlands; Horama, Paris, France; Eyevensys, Paris, France; Nayan, Seattle, WA; SparingVision, Paris, France; AGTC, Alachua, FL; and Sanofi, Paris, France outside the submitted work; personal fees and other from Nacuity, Fort Worth, TX; Ocugen, Malvern, PA; and Vedere Bio, Cambridge, MA. M. Michaelides reports personal fees from MeiraGTx, Stargazer Pharma, Acucela, Astellas, ProQR, and 2CTech, outside the submitted work; and Stock options with MeiraGTx, New York, NY. G. Jaffe reports other from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research; other from Novartis, Basel, Switzerland during the conduct of the study. I. Audo reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study. C. Kay reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study A. Ayala, T. Durham, R. Hufnagel, F. Ferris, E. Heon, and W. Liang have no financial disclosures. Funding Information: All authors attest that they meet the current ICMJE criteria for authorship. Foundation Fighting Blindness (FFB) Consortium: David Birch is supported by NIH grant EY009076. Isabelle Audo is a member of the French National Rare Diseases network of the eye and the ear, SENSGENE, and the ERN-EYE (European Reference Network for Rare Eye Diseases) and is supported by RHU-Light4deaf [ANR-15-RHU-0001] and IHU FOReSIGHT [ANR-18-IAHU-0001] supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program . Jacque Duncan is supported by Research to Prevent Blindness (UCSF). Alessandro Iannaccone is supported by an unrestricted departmental grant to the Duke Eye Center from Research to Prevent Blindness, New York, NY. Michel Michaelides is supported by a grant from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology. Mark Pennesi is supported by an unrestricted grant from RPB to Casey Eye Institute and a core grant NIH P30EY010572. Funding Information: Funding/Support: This work was supported by funds from the Foundation Fighting Blindness, Columbia, MD, USA. Financial Disclosures: J. Cheetham reports personal fees from Foundation Fighting Blindness, Columbia, MD, and personal fees from Allergan, Dublin IR. L. Erker reports grants from the NIH, Bethesda, MD; FDA Orphan, Silver Spring, MD; Department of Defense Grant, VA; and Wynn Gund grant, from Foundation Fighting Blindness during the conduct of the study; other relevant conflict of interest from Sanofi, Paris, France; Applied Genetic Technologies Corporation, Alachua, FL; Meira Gtx, New York, NY, NightstaRx, London, UK; and Novelion, Vancouver, BC, Canada. S. Degli Esposti reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and receives personal fees from GSK, UK; Novartis, UK; Bayer, UK; and Allergan, UK, outside the submitted work. M. Maguire reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research. J. Duncan reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; personal fees from 4D Therapeutics, Emeryville, CA; Applied Genetic Technologies Corporation, Alachua, FL; Editas Medicine, Inc, Cambridge, MA; Biogen/NightstaRx Therapeutics, London, UK; ProQR Therapeutics, Leiden, Netherlands; Spark Therapeutics, Philadelphia, PA; SparingVision, Paris, France; Vedere Bio, Cambridge, MA; Horama, Paris, France; grants from Foundation Fighting Blindness, Columbia, MD; Research to Prevent Blindness, New York, NY; National Eye Institute, Bethesda, MD; and personal fees from Miller Medical Communications, New York, NY, outside the submitted work. A. Iannaccone reports grants and personal fees from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study; personal fees from Alia Therapeutics, Trento, Italy; ClearViewHealthcare Partners, Newton, MA; Teladoc Health, Westwood, MA; GLG Group, San Francisco, CA; Guidepoint, Boston, MA; Astellas Institute for Regenerative Medicine, Marlborough, MA; Roivant Pharma, New York, NY; Editas Medicine, Cambridge, MA; Rhythm Pharmaceuticals, Boston, MA; IQVIA, Durham, NC; Gyroscope, Stevenage, UK; and Ocugen, Malvern, PA; grants from AGTC, Alachua, FL; Allergan, Dublin, Ireland; Acucela, Seattle, WA; ProQR, Leiden, Netherlands; Retinagenix, Seattle, WA; and 4D Molecular Therapeutics, Emeryville, CA outside the submitted work. D. Birch reports grants and personal fees from Foundation Fighting Blindness, Columbia, MD, and grant EY009076 from NIH, Bethesda, MD, during the conduct of the study; personal fees from ProQR, Leiden, Netherlands; Nacuity, Fort Worth, TX; AGTC, Alachua, FL; and Editas, Cambridge, MA, outside the submitted work. S. Farsiu reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; grants from Foundation Fighting Blindness, Columbia, MD, outside the submitted work; and Duke University, Durham, NC; he has developed DOCTRAP software, a version of which is used for this study. This software is also used in other studies that are sponsored by external entities that pay Duke in form of research grants or contracts. Part of his compensation and research funds comes from such activities. J. Sahel reports grants from LabEx LIFESENSES (ANR-10-LABX-65), Paris, France; and grants from IHU FOReSIGHT (ANR-18-IAHU-01), Paris, France, during the conduct of the study. J. Carroll reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study and personal fees from MeiraGTx outside the submitted work. M. Pennesi reports grants from Foundation Fighting Blindness, Columbia, MD, during the conduct of the study; consulting fees from Allergan/Editas, Cambridge, MA; Spark Therapeutics, Philadelphia, PA; Wave Biosciences, Cambridge, MA; Astellas Pharmaceuticals, Chuo City, Tokyo, Japan; RegenexBio, Rockville, MD; and Iveric, New York, NY; other from Biogen, Cambridge, MA; Novartis, Basel, Switzerland; Adverum, Redwood City, CA; Gensight, Paris, France; ProQR, Leiden, Netherlands; Horama, Paris, France; Eyevensys, Paris, France; Nayan, Seattle, WA; SparingVision, Paris, France; AGTC, Alachua, FL; and Sanofi, Paris, France outside the submitted work; personal fees and other from Nacuity, Fort Worth, TX; Ocugen, Malvern, PA; and Vedere Bio, Cambridge, MA. M. Michaelides reports personal fees from MeiraGTx, Stargazer Pharma, Acucela, Astellas, ProQR, and 2CTech, outside the submitted work; and Stock options with MeiraGTx, New York, NY. G. Jaffe reports other from Foundation Fighting Blindness, Columbia, MD, via the Jaeb Center for Health Research; other from Novartis, Basel, Switzerland during the conduct of the study. I. Audo reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study. C. Kay reports grants from Foundation Fighting Blindness Consortium, Columbia, MD, during the conduct of the study A. Ayala, T. Durham, R. Hufnagel, F. Ferris, E. Heon, and W. Liang have no financial disclosures. All authors attest that they meet the current ICMJE criteria for authorship. Foundation Fighting Blindness (FFB) Consortium: David Birch is supported by NIH grant EY009076. Isabelle Audo is a member of the French National Rare Diseases network of the eye and the ear, SENSGENE, and the ERN-EYE (European Reference Network for Rare Eye Diseases) and is supported by RHU-Light4deaf [ANR-15-RHU-0001] and IHU FOReSIGHT [ANR-18-IAHU-0001] supported by French state funds managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program. Jacque Duncan is supported by Research to Prevent Blindness (UCSF). Alessandro Iannaccone is supported by an unrestricted departmental grant to the Duke Eye Center from Research to Prevent Blindness, New York, NY. Michel Michaelides is supported by a grant from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology. Mark Pennesi is supported by an unrestricted grant from RPB to Casey Eye Institute and a core grant NIH P30EY010572. Acknowledgments: Foundation Fighting Blindness (FFB) Consortium Contributors to the RUSH2A Protocol. FFB Consortium Clinical Sites: Clinical sites participating in this protocol are listed in order by number of participants enrolled into the study. The number of participants enrolled is noted in parentheses preceded by the site location and the site name. Personnel are listed as (I) for Study Investigator, (C) for Coordinator, and (T) for Technician. San Francisco, CA - UCSF Department of Ophthalmology (18): Jacque Duncan (I), Arshia Mian (C), Yiran Liu (C), Mary Lew (C, T), John Peterson (T), Tom Hernandez (T), Betty Hom (T), Hoover Chan (T). Portland, OR - Oregon Health & Science University (14): Mark Pennesi (I), Paul Yang (I), Annelise Haft (C,T), Jordan Barth (T), Chiedozie Ukachukwu (T), Gareth Harman (T), Jocelyn Hui (T), Jennifer Hilgeman (T), Virinda Boyle (T), Scott Pickell (T), Darius Liseckas (T). London, United Kingdom - Moorfields Eye Hospital (13): Michel Michaelides (I), Simona Delgi Esposti (I), Shweta Anand (I), William Tucker (I), Tabassum Master (C), Emma Treacy (C), Alexa King (C), Samiul Rahman (C), Tina Reetun (C), Emerson Tingco (C, T), Katherine Binstead (T), Sash Yoganand Jeetun (T), Nafaz Mohamed Illyias (T), Linda Burton (T), Selma Lewis (T), Graham Brown (T), Gareth Davey (T), Kanom Bibi (T), Vincent Rocco (T), Shabneez Laulloo (T), Tran Dang (T), Andrew Carter (T), Anne Georgiou (T), MinakoLisa Nathasingh (T). Nijmegen, Netherlands - Radboud University Medical Center (13): Carel Hoyng (I), Jack Weeda (C,T), Esmee Runhart (C), Hans Hermens (T). Paris, France - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DGOS CIC1423 (13): Jose-Alain Sahel (I), Saddek Mohand-Said (I), Isabelle Audo (I), Pierre Queromes (I), Celine Devisme (C), Charl?ne Da Silveira (C), Carole Romand (C), Serge Sancho (T), Sarah Baranes (T), Mathias Chapon (T), Juliette Amaudruz (T), C?line Chaumette (T), Aurore Girmens (T), Victoria Ganem (T). Dallas, TX - Retina Foundation of the Southwest (12): David Birch (I), Martin Klein (C, T), Kirsten Locke (C,T). Tubingen, Germany - Center for Ophthalmology/Clinic for Hereditary Retina Degenerations, University of T?bingen (11): Katarina Stingl (I), Laura Kuehlewein (I), Andrea Rindtorff (C,T), Benjamin-Phillip Beier (C,T), Gudrun H?rer (T), Michael Breuninger (T), Susanne Schweyer (T), Ulrike Fuchs (T), Susanne Kramer (T). Ann Arbor, MI - University of Michigan, Kellogg Eye Center (9): Thiran Jayasundera (I), Naheed W. Khan (I), Abigail Fahim (I), Kari Branham (I), Munira Hussain (C,T), Cailyn Wolford (C,T), Lindsay Godsey (C,T), Laura Trebesh (T), Kit Morehead (T). Boston, MA - Massachusetts Eye and Ear Infirmary (8): Rachel Huckfeldt (I), Tu Doan (C), Xiao-Hong Wen (C), John Hensel (T), Bethany Biron (T), Jasmeet Bhullar (T), Lisa Dennehy (T), Matthew DiRocco (T), Sarah Brett (T), Emorfily Potsidis (T), Yuji Che (T). Gainesville, FL - Vitreo Retinal Associates, P.A. (7): Christine Kay (I), Jing Zhang (C,T). Houston, TX - Baylor College of Medicine, Alkek Eye Center (7): John Timothy Stout (I), Tahira Scholle (I), Annika Joshi (C,T), Joseph Morales (T), Dana Barnett (T), Laine Maier (T). Durham, NC - Duke University Medical Center (6): Alessandro Iannaccone (I), Elmer Balajonda (C), Magaly Guerrero (C,T), Amy Clark (C,T), Victoria Griffiths (T), Ryan Imperio (T), Malina Sexton (T), Alexandra Bosquet (T), Marina Kedrov (T), Brian Lutman (T). Baltimore, MD - Johns Hopkins University Hospital, Wilmer Eye Institute (5): Mandeep Singh (I), Mary Frey (C,T), David Emmert (T), Mohamed Ahmed (T), Lisa Liberto (T), Jennifer Bassinger (T). Salt Lake City, UT - University of Utah, John Moran Eye Center (4): Paul Bernstein (I), Kara Halsey (C), Donnell Creel (T), Kelliann Farnsworth (T), Danielle Wiscombe (T), William Hubbard (T). Toronto, Canada - University of Toronto, Hospital for Sick Children (4): Elise Heon (I), Vaishnavi Batmanabane (C,T), Katelyn Macneill (T), Jeff Locke (T), Ajoy Vincent (I). Milwaukee, WI - The Medical College of Wisconsin Eye Institute (1): Thomas Connor, Jr (I), William Wirostko (I), Katie McKenney (C,T), Amber Roberts (T). FFB Consortium Coordinating Center: Jaeb Center for Health Research, Tampa, FL (staff as of 02/25/2020): Ken Arcieri, Allison Ayala, Elizabeth Caruana, Peiyao Cheng, Jennifer Kennedy, Nadine Label, Stephanie Lee, Wendi Liang, Olivia Parrillo, Rebecca Parsons, Elizabeth Smith. Casey Reading Center [CRC], Casey Eye Institute, Oregon Health Sciences University, Portland, OR (Electroretinography, Static Perimetry, and Kinetic Perimetry): Ellie Chegarnov, Laura Erker, Melissa Krahmer, Brandon Lujan, Audra Miller, Albert Romo, Edeleidys Sanchez Saucedo. Duke Reading Center [DRC], Duke University, Durham, NC (Optical Coherence Tomography and Microperimetry): Vivienne Fang, Sina Farsiu, Magaly Guerrero, Cynthia Heydary, Grace Huh, Glenn Jaffe, Leon Kwark, Eleonora Lad, Brittany Mullaney, Justin Myers, Jayne Nicholson, Katrina Winter. FFB Consortium Genetics Committee: Kari Branham, Stephen Daiger, Robert Hufnagel. FFB Consortium Executive Committee: Jacque Duncan (Chair), Allison Ayala, David Birch, Janet Cheetham, Todd Durham, Rick Ferris, Maureen Maguire, Mark Pennesi. FFB Consortium Audiology Reviewer: Carmen Brewer. Publisher Copyright: © 2020 Elsevier Inc.

PY - 2020/11

Y1 - 2020/11

N2 - Purpose: To report baseline visual fields in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study. Design: Cross-sectional study within a natural history study. Methods: Setting: multicenter, international. Study population: Usher syndrome type 2 (USH2) (n = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) (n = 47) associated with biallelic disease-causing sequence variants in USH2A. Observation procedures: Repeatability of full-field static perimetry (SP) and between-eye symmetry of kinetic perimetry (KP) were evaluated with intraclass correlation coefficients (ICCs). The association of demographic and clinical characteristics with total hill of vision (VTOT) was assessed with general linear models. Associations between VTOT and other functional and morphologic measures were assessed using Spearman correlation coefficients and t tests. Main outcome measures: VTOT (SP) and III4e isopter area (KP). Results: USH2 participants had more severe visual field loss than ARRP participants (P < .001, adjusting for disease duration, age of enrollment). Mean VTOT measures among 3 repeat tests were 32.7 ± 24.1, 31.2 ± 23.4, and 31.7 ± 23.9 decibel-steradians (intraclass correlation coefficient [ICC] = 0.96). Better VA, greater photopic ERG 30-Hz flicker amplitudes, higher mean microperimetry sensitivity, higher central subfield thickness, absence of macular cysts, and higher III4e seeing area were associated with higher VTOT (all r > .48; P < .05). Mean III4e isopter areas for left (4561 ± 4426 squared degrees) and right eyes (4215 ± 4300 squared degrees) were concordant (ICC = 0.94). Conclusions: USH2 participants had more visual field loss than participants with USH2A-related ARRP, adjusting for duration of disease and age of enrollment. VTOT was repeatable and correlated with other functional and structural metrics, suggesting it may be a good summary measure of disease severity in patients with USH2A-related retinal degeneration.

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

UR - http://www.scopus.com/inward/record.url?scp=85089292776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85089292776&partnerID=8YFLogxK

U2 - 10.1016/j.ajo.2020.05.024

DO - 10.1016/j.ajo.2020.05.024

M3 - Article

C2 - 32446738

AN - SCOPUS:85089292776

SN - 0002-9394

VL - 219

SP - 87

EP - 100

JO - American journal of ophthalmology

JF - American journal of ophthalmology

ER -

Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity

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