TY - JOUR
T1 - The role of dark adaptation in understanding early AMD
AU - Murray, Ian J.
AU - Rodrigo-Diaz, Elena
AU - Kelly, Jeremiah M.F.
AU - Tahir, Humza J.
AU - Carden, David
AU - Patryas, Laura
AU - Parry, Neil RA
N1 - Funding Information:
NRAP is supported by Manchester Biomedical Research Centre and the Greater Manchester Comprehensive Local Research Network.
Funding Information:
Some of this work was supported by Newtricious R&D B.V. (HJT and ER) and by The National Eye Research Centre (ER). The NIHR Invention for Innovation (i4i) Programme funded the clinical trial and JK.
Funding Information:
NRAP is supported by Manchester Biomedical Research Centre and the Greater Manchester Comprehensive Local Research Network. Some of this work was supported by Newtricious R&D B.V. (HJT and ER) and by The National Eye Research Centre (ER). The NIHR Invention for Innovation (i4i) Programme funded the clinical trial and JK. IJM, DC and JK are directors of MuMac Research who developed the RapiDA technique. We sincerely thank the reviewers for carefully reading the paper and for their many insightful comments.
Publisher Copyright:
© 2021
PY - 2021
Y1 - 2021
N2 - The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD. Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time. Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.
AB - The main aim of the paper is to discuss current knowledge on how Age Related Macular Degeneration (AMD) affects Dark Adaptation (DA). The paper is divided into three parts. Firstly, we outline some of the molecular mechanisms that control DA. Secondly, we review the psychophysical issues and the corresponding analytical techniques. Finally, we characterise the link between slowed DA and the morphological abnormalities in early AMD. Historically, DA has been regarded as too cumbersome for widespread clinical application. Yet the technique is extremely useful; it is widely accepted that the psychophysically obtained slope of the second rod-mediated phase of the dark adaptation function is an accurate assay of photoreceptor pigment regeneration kinetics. Technological developments have prompted new ways of generating the DA curve, but analytical problems remain. A simple potential solution to these, based on the application of a novel fast mathematical algorithm, is presented. This allows the calculation of the parameters of the DA curve in real time. Improving current management of AMD will depend on identifying a satisfactory endpoint for evaluating future therapeutic strategies. This must be implemented before the onset of severe disease. Morphological changes progress too slowly to act as a satisfactory endpoint for new therapies whereas functional changes, such as those seen in DA, may have more potential in this regard. It is important to recognise, however, that the functional changes are not confined to rods and that building a mathematical model of the DA curve enables the separation of rod and cone dysfunction and allows more versatility in terms of the range of disease severity that can be monitored. Examples are presented that show how analysing the DA curve into its constituent components can improve our understanding of the morphological changes in early AMD.
KW - Dark adaptation
KW - Drusen
KW - Early/intermediate AMD
KW - Rhodopsin regeneration
KW - Sensitivity control
KW - Structure versus function
UR - http://www.scopus.com/inward/record.url?scp=85117222453&partnerID=8YFLogxK
U2 - 10.1016/j.preteyeres.2021.101015
DO - 10.1016/j.preteyeres.2021.101015
M3 - Article
AN - SCOPUS:85117222453
SN - 1350-9462
JO - Progress in Retinal and Eye Research
JF - Progress in Retinal and Eye Research
M1 - 101015
ER -