Article Retinal Differential Light Sensitivity Variation Across the Macula in Healthy Subjects: Importance of Cone Separation and Loci Eccentricity Danuta M. Sampson 1,2,* , Danial Roshandel 1,* , Avenell L. Chew 1 , Yufei Wang 3 , Paul G. Stevenson 4 , Matthew N. Cooper 4 , Elaine Ong 1 , Lawrence Wong 1 , Jonathan La 1 , David Alonso-Caneiro 1,5 , Enid Chelva 6 , Jane C. Khan 1,7 , David D. Sampson 8 , and Fred K. Chen 1,7 1 Centre for Ophthalmology and Visual Science (Incorporating Lions Eye Institute), The University of Western Australia, Nedlands, Western Australia, Australia 2 Surrey Biophotonics, Centre for Vision, Speech and Signal Processing and School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom 3 Computer Science Department, University of Wisconsin-Madison, Madison, WI, USA 4 Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia 5 Contact Lens and Visual Optics Laboratory, School of Optometry and Vision Science, Queensland University of Technology, Queensland, Australia 6 Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia 7 Department of Ophthalmology, Royal Perth Hospital, Perth, Western Australia, Australia 8 Surrey Biophotonics, School of Physics and School of Biosciences and Medicine, University of Surrey, Guildford, UK Correspondence: Fred K. Chen, Lions Eye Institute, 2 Verdun Street, Nedlands 6009, Western Australia, Australia. e-mail: fredchen@lei.org.au Received: November 3, 2020 Accepted: March 29, 2021 Published: May 11, 2021 Keywords: photoreceptors; adaptive optics retinal imaging; microperimetry; retinal structure-function structure; normative data Citation: Sampson DM, Roshandel D, Chew AL, Wang Y, Stevenson PG, Cooper MN, Ong E, Wong L, La J, Alonso-Caneiro D, Chelva E, Khan JC, Sampson DD, Chen FK. Retinal differential light sensitivity variation across the macula in healthy subjects: Importance of cone separation and loci eccentricity. Transl Vis Sci Technol. 2021;10(6):16, https://doi.org/10.1167/tvst.10.6.16 Purpose: Microperimetry measures differential light sensitivity (DLS) at specific retinal locations. The aim of this study is to examine the variation in DLS across the macula and the contribution to this variation of cone distribution metrics and retinal eccentricity. Methods: Forty healthy eyes of 40 subjects were examined by microperimetry (MAIA) and adaptive optics imaging (rtx1). Retinal DLS was measured using the grid patterns: foveal (2°–3°), macular (3°–7°), and meridional (2°–8° on horizontal and vertical meridi- ans). Cone density (CD), distribution regularity, and intercone distance (ICD) were calcu- lated at the respective test loci coordinates. Linear mixed-effects regression was used to examine the association between cone distribution metrics and loci eccentricity, and retinal DLS. Results: An eccentricity-dependent reduction in DLS was observed on all MAIA grids, which was greatest at the foveal-parafoveal junction (2°–3°) (−0.58 dB per degree, 95% confidence interval [CI]; −0.91 to −0.24 dB, P < 0.01). Retinal DLS across the meridional grid changed significantly with each 1000 cells/deg 2 change in CD (0.85 dB, 95% CI; 0.10 to 1.61 dB, P = 0.03), but not with each arcmin change in ICD (1.36 dB, 95% CI; −2.93 to 0.20 dB, P = 0.09). Conclusions: We demonstrate significant variation in DLS across the macula. Topographical change in cone separation is an important determinant of the variation in DLS at the foveal-parafoveal junction. We caution the extrapolation of changes in DLS measurements to cone distribution because the relationship between these variables is complex. Translational Relevance: Cone density is an independent determinant of DLS in the foveal-parafoveal junction in healthy eyes. Copyright 2021 The Authors tvst.arvojournals.org | ISSN: 2164-2591 1 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Downloaded from tvst.arvojournals.org on 05/17/2021