Philipp L Müller1, Martin Gliem2, Myra McGuinnes3, Johannes Birtel4, Frank G Holz2, Peter Charbel Issa5. 1. Department of Ophthalmology, University of Bonn, Bonn, Germany; Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany; Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. 2. Department of Ophthalmology, University of Bonn, Bonn, Germany; Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany. 3. Department of Ophthalmology, University of Bonn, Bonn, Germany; Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia. 4. Department of Ophthalmology, University of Bonn, Bonn, Germany; Center for Rare Diseases Bonn (ZSEB), University of Bonn, Bonn, Germany; Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. 5. Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. Electronic address: study-enquiry@outlook.com.
Abstract
PURPOSE: To investigate lipofuscin-related quantitative autofluorescence measures and their association with demographic characteristics, retinal structure, retinal function and genotype in ABCA4-related retinopathy (Stargardt disease 1). DESIGN: Cross-sectional study with age-matched healthy control subjects. METHODS: A total of 77 patients with ABCA4-related retinopathy and 110 control subjects underwent quantitative fundus autofluorescence (qAF) imaging using a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to measure qAF as surrogate for lipofuscin accumulation. Measures of qAF were correlated with demographic characteristics, structural alterations on optical coherence tomography and fundus autofluorescence imaging, retinal function assessed by full-field electroretinography (ERG) and fundus-controlled perimetry, and genotype. RESULTS: Most patients (76.6%) had qAF levels >95% prediction interval of the age-related control group, with best discrimination between cases and control subjects in younger patients. Reduced discrimination based on qAF measures was associated with mild disease, more advanced disease with dark flecks, or older age because of the physiological age-related increase in qAF and a ceiling effect in patients. Nullizygous patients presented with high qAF levels earlier in life compared with those with at least 1 milder ABCA4 variant. Within the sectors of qAF measurements, at approximately 7-9° eccentricity, increased qAF without flecks or with only bright flecks was associated with topographically related preserved retinal thickness and fundus-controlled perimetry results, and with normal full-field ERG recordings. All 3 parameters were increasingly abnormal with the development of dark flecks and decreasing qAF. CONCLUSIONS: The accumulation of lipofuscin depends on the severity of ABCA4 variants, precedes other structural changes, and may remain without clinically relevant effect on retinal function.
PURPOSE: To investigate lipofuscin-related quantitative autofluorescence measures and their association with demographic characteristics, retinal structure, retinal function and genotype in ABCA4-related retinopathy (Stargardt disease 1). DESIGN: Cross-sectional study with age-matched healthy control subjects. METHODS: A total of 77 patients with ABCA4-related retinopathy and 110 control subjects underwent quantitative fundus autofluorescence (qAF) imaging using a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to measure qAF as surrogate for lipofuscin accumulation. Measures of qAF were correlated with demographic characteristics, structural alterations on optical coherence tomography and fundus autofluorescence imaging, retinal function assessed by full-field electroretinography (ERG) and fundus-controlled perimetry, and genotype. RESULTS: Most patients (76.6%) had qAF levels >95% prediction interval of the age-related control group, with best discrimination between cases and control subjects in younger patients. Reduced discrimination based on qAF measures was associated with mild disease, more advanced disease with dark flecks, or older age because of the physiological age-related increase in qAF and a ceiling effect in patients. Nullizygous patients presented with high qAF levels earlier in life compared with those with at least 1 milder ABCA4 variant. Within the sectors of qAF measurements, at approximately 7-9° eccentricity, increased qAF without flecks or with only bright flecks was associated with topographically related preserved retinal thickness and fundus-controlled perimetry results, and with normal full-field ERG recordings. All 3 parameters were increasingly abnormal with the development of dark flecks and decreasing qAF. CONCLUSIONS: The accumulation of lipofuscin depends on the severity of ABCA4 variants, precedes other structural changes, and may remain without clinically relevant effect on retinal function.
Authors: Patty P A Dhooge; Esmee H Runhart; Stanley Lambertus; Nathalie M Bax; Johannes M M Groenewoud; B Jeroen Klevering; Carel B Hoyng Journal: Transl Vis Sci Technol Date: 2021-03-01 Impact factor: 3.283
Authors: Maximilian Pfau; Catherine A Cukras; Laryssa A Huryn; Wadih M Zein; Ehsan Ullah; Marisa P Boyle; Amy Turriff; Michelle A Chen; Aarti S Hinduja; Hermann Ea Siebel; Robert B Hufnagel; Brett G Jeffrey; Brian P Brooks Journal: JCI Insight Date: 2022-01-25
Authors: Katie M Williams; Michalis Georgiou; Angelos Kalitzeos; Isabelle Chow; Pirro G Hysi; Anthony G Robson; Gareth Lingham; Fred K Chen; David A Mackey; Andrew R Webster; Christopher J Hammond; Polina Prokhoda; Joseph Carroll; Michel Michaelides; Omar A Mahroo Journal: Invest Ophthalmol Vis Sci Date: 2022-06-01 Impact factor: 4.925
Authors: Rachael C Heath Jeffery; Jennifer A Thompson; Johnny Lo; Tina M Lamey; Terri L McLaren; Ian L McAllister; David A Mackey; Ian J Constable; John N De Roach; Fred K Chen Journal: Ophthalmol Sci Date: 2021-03-06