{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:58:57Z","timestamp":1779897537805,"version":"3.53.1"},"reference-count":72,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205174\/Z\/16\/Z"],"award-info":[{"award-number":["205174\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography underlying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diameter. Thirty-two eyes from 16 patients (mean age \u00b1 SD, 36.0 \u00b1 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial alignment was observed between IR-EZ and OR-ELM diameters\/widths (p &lt; 0.001). The IMPM border occurred just lateral to EZ loss (p &lt; 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 \u03bcm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p &lt; 0.001). As the strongest correlate of cone density (p &lt; 0.001) and best-corrected visual acuity (p &lt; 0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint.<\/jats:p>","DOI":"10.3390\/ijms23084198","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:23:11Z","timestamp":1649722991000},"page":"4198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Investigating Biomarkers for USH2A Retinopathy Using Multimodal Retinal Imaging"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3705-6000","authenticated-orcid":false,"given":"Jasdeep S.","family":"Gill","sequence":"first","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Theofylaktopoulos","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Mitsios","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"},{"name":"NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Houston","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Hagag","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"},{"name":"NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-2179","authenticated-orcid":false,"given":"Adam M.","family":"Dubis","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"},{"name":"NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Global Business School for Health, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London EC1V 9EL, UK"},{"name":"NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/0021-9681(83)90147-9","article-title":"Usher syndrome: Definition and estimate of prevalence from two high-risk populations","volume":"36","author":"Boughman","year":"1983","journal-title":"J. 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