Philipp L Müller1, Tim Treis2, Maximilian Pfau3, Simona Degli Esposti4, Abdulrahman Alsaedi5, Peter Maloca6, Konstantinos Balaskas4, Andrew Webster7, Catherine Egan7, Adnan Tufail8. 1. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Department of Ophthalmology, University of Bonn, Bonn, Germany; Center for Rare Diseases, University of Bonn, Bonn, Germany. 2. BioQuant, University of Heidelberg, Heidelberg, Germany. 3. Department of Ophthalmology, University of Bonn, Bonn, Germany; Department of Biomedical Data Science, Stanford University, Stanford, California, USA. 4. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. 5. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia. 6. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Institute of Molecular and Clinical Ophthalmology (IOB), Basel, Switzerland; OCTlab, Department of Ophthalmology, University Hospital Basel, Basel, Switzerland. 7. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom. 8. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; Institute of Ophthalmology, University College London, London, United Kingdom. Electronic address: adnan.tufail@nhs.net.
Abstract
PURPOSE: To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to maternally inherited diabetes and deafness (MIDD) and to evaluate the application of these factors in clinical trial design. DESIGN: Retrospective observational case series. METHODS: Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by 2 independent readers. A linear mixed-effect 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: The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm2/year, revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm2/year/mm2, P < .001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials. CONCLUSIONS: Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design.
PURPOSE: To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to maternally inherited diabetes and deafness (MIDD) and to evaluate the application of these factors in clinical trial design. DESIGN: Retrospective observational case series. METHODS: Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by 2 independent readers. A linear mixed-effect 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: The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm2/year, revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm2/year/mm2, P < .001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials. CONCLUSIONS: Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design.
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: 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
Authors: Jin Kyun Oh; Jose Ronaldo Lima de Carvalho; Yan Nuzbrokh; Joseph Ryu; Teja Chemudupati; Vinit B Mahajan; Janet R Sparrow; Stephen H Tsang Journal: Invest Ophthalmol Vis Sci Date: 2020-10-01 Impact factor: 4.799