Philipp L Müller1,2,3, Maximilian Pfau1, Tim Treis4, Isabel Pascual-Camps5, Johannes Birtel1,2, Moritz Lindner1,6, Philipp Herrmann1,2, Frank G Holz1,2. 1. Department of Ophthalmology, University of Bonn, Bonn, Germany. 2. Center for Rare Diseases, University of Bonn, Bonn, Germany. 3. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. 4. BioQuant, University of Heidelberg, Heidelberg, Germany. 5. FISABIO Oftalmología Médica, Valencia, Spain; and. 6. Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
Abstract
PURPOSE: To investigate the prognostic value of demographic, functional, genetic, and imaging parameters on retinal pigment epithelium atrophy progression secondary to ABCA4-related retinopathy. METHODS: Patients with retinal pigment epithelium atrophy secondary to ABCA4-related retinopathy were examined longitudinally with fundus autofluorescence imaging. Lesion area, perimeter, circularity, caliper diameters, and focality of areas with definitely decreased autofluorescence were determined. A model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: Sixty-eight eyes of 37 patients (age range, 14-78 years) with a follow-up time of 10 to 100 months were included. The mean annual progression of retinal pigment epithelium atrophy was 0.89 mm. The number of atrophic areas, the retina-wide functional impairment, and the age-of-onset category constituted significant predictors for future retinal pigment epithelium atrophy growth, explaining 25.7% of the variability. By extension of a simulated study length and/or specific patient preselection based on these baseline characteristics, the required sample size could significantly be reduced. CONCLUSION: Trial design based on specific shape-descriptive factors and patients' baseline characteristics and the adaption of the trial duration may provide potential benefits in required cohort size and absolute number of visits.
PURPOSE: To investigate the prognostic value of demographic, functional, genetic, and imaging parameters on retinal pigment epithelium atrophy progression secondary to ABCA4-related retinopathy. METHODS:Patients with retinal pigment epithelium atrophy secondary to ABCA4-related retinopathy were examined longitudinally with fundus autofluorescence imaging. Lesion area, perimeter, circularity, caliper diameters, and focality of areas with definitely decreased autofluorescence were determined. A model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: Sixty-eight eyes of 37 patients (age range, 14-78 years) with a follow-up time of 10 to 100 months were included. The mean annual progression of retinal pigment epithelium atrophy was 0.89 mm. The number of atrophic areas, the retina-wide functional impairment, and the age-of-onset category constituted significant predictors for future retinal pigment epithelium atrophy growth, explaining 25.7% of the variability. By extension of a simulated study length and/or specific patient preselection based on these baseline characteristics, the required sample size could significantly be reduced. CONCLUSION: Trial design based on specific shape-descriptive factors and patients' baseline characteristics and the adaption of the trial duration may provide potential benefits in required cohort size and absolute number of visits.
Authors: Philipp L Müller; Alexandru Odainic; Tim Treis; Philipp Herrmann; Adnan Tufail; Frank G Holz; Maximilian Pfau Journal: Sci Rep Date: 2021-01-14 Impact factor: 4.379
Authors: Philipp L Müller; Bart Liefers; Tim Treis; Filipa Gomes Rodrigues; Abraham Olvera-Barrios; Bobby Paul; Narendra Dhingra; Andrew Lotery; Clare Bailey; Paul Taylor; Clarisa I Sánchez; Adnan Tufail 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: Rachael C Heath Jeffery; Jennifer A Thompson; Johnny Lo; Tina M Lamey; Terri L McLaren; John N De Roach; Dimitar N Azamanov; Ian L McAllister; Ian J Constable; Fred K Chen Journal: Retina Date: 2022-04-24 Impact factor: 3.975
Authors: Philipp L Müller; Tim Treis; Alexandru Odainic; Maximilian Pfau; Philipp Herrmann; Adnan Tufail; Frank G Holz Journal: J Clin Med Date: 2020-07-29 Impact factor: 4.241