Are Current Methods of Measuring Dark Adaptation Effective in Detecting the Onset and Progression of Age-Related Macular Degeneration? A Systematic Literature Review

Abstract

Introduction: Dark adaptation (DA) has been proposed as a possible functional biomarker for age-related macular degeneration (AMD). In this systematic review we aim to evaluate current methodology used to assess DA in people with AMD, the evidence of precision in detecting the onset and progression of AMD, and the relationship between DA and other functional and structural measures. Methods: MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, PsycARTICLES were searched for studies published between January 2006 and January 2020 that assessed DA in people with AMD. Details of eligible studies including study design, characteristics of study population and outcomes were recorded. All included studies underwent quality appraisal using approved critical appraisal tools. This systematic review follows PRISMA guidelines (PROSPERO registration number: CRD42019129486). Results: Forty-eight studies were eligible for inclusion, reporting a variety of instruments and protocols to assess different DA parameters. Twenty of these studies used the AdaptDx (MacuLogix, Hummelstown, PA, USA) instrument and assessed rod-intercept time (RIT). Most of these reported that RIT was delayed in people with AMD and this delay worsened with AMD severity. Four studies, involving 533 participants, reported estimates of diagnostic performance of AdaptDx to separate people with AMD from visually healthy controls. DA has been compared to other measures of visual function, patient-reported outcome measures (PROMs) and structural measures. Ten studies specifically considered evidence that the presence of certain structural abnormalities was associated with impaired DA in AMD. Conclusions: This systematic review indicates overwhelming evidence of reasonable quality for an association between impaired DA and AMD. Data on the repeatability and reproducibility of DA measurement are sparse. There is evidence that structural abnormalities such as reticular drusen are associated with prolongation of DA time. Fewer studies have explored an association between DA and other measures of visual function or PROMs. We found no studies that had compared DA with performance-based measures.

Test-Retest Variability and Discriminatory Power of Measurements From Microperimetry and Dark Adaptation Assessment in People With Intermediate Age-Related Macular Degeneration – A MACUSTAR Study Report

“…Elsewhere in the literature, there is overwhelming evidence of an association between impaired dark adaptation and AMD but the studies of the discrimination performance of RIT in separating people with different levels of AMD are limited. 10 Good levels of test-retest variability of the S-MAIA (both mesopic and scotopic conditions) have been previously reported using CoR metrics. For example, Welker et al (2018) reported CoR of 4.4 dB (mesopic) and 4.52 dB (scotopic) for pointwise sensitivity in a small number ( n = 23) of volunteers with iAMD.…”

“…Assessment of test-retest variability for a device in small numbers of visually healthy people is inadequate. For instance, in a recent systematic review of the measurement of dark adaptation, with a focus on the AdaptDx device, 10 we found only one study to have adequately attempted to assess test-retest variability and this did not specify the disease status of the cohort recruited. 11 Better reports on the topic for measurements from S-MAIA exist.…”

Dark Adaptation and Its Role in Age-Related Macular Degeneration

“…There are many excellent resources by eminent authors that describe visual changes during dark and light adaptation [ 6 ] visual function and functional vision in presence of aging and early AMD [ 7 , 8 , 9 ]. A recent literature review focuses on the effectiveness of current DA measuring methods in detecting onset and progression of AMD [ 10 ], however a specific focus on clinical aspects of DA measurement and its significance to furthering our understanding of AMD integrating physiological aspects of DA, AMD pathophysiology, significance of DA as a functional biomarker, different methodologies and correlation of DA with patient reported outcome measures (PROMs), has been an important area of development. Given the wealth of research studies in recent years specifically related to DA and AMD, this review article is timely.…”

Assessment of the Classification of Age-Related Macular Degeneration Severity from the Northern Ireland Sensory Ageing Study Using a Measure of Dark Adaptation

“…OCT has many advantages over CFP, such as better differentiating between structural abnormalities such as SDDs 21 in three-dimensions 26 . Our recent systematic literature review 27 highlighted OCTbased studies that have revealed new relationships between AMD macular anatomy (such as SDDs) and RMDA 6,8,25,28,29 . However, the sample sizes of the SDD cohorts (n=<20) 6,8,25 have been small and few included age-adjusted control groups.…”