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Aspects of Measuring Dark Adaptation in People with Age-Related Macular Degeneration

Higgins, Bethany (2022). Aspects of Measuring Dark Adaptation in People with Age-Related Macular Degeneration. (Unpublished Doctoral thesis, City, University of London)


In age-related macular degeneration (AMD) research, dark adaptation (DA) has been found to be a promising functional measurement and a potential biomarker for AMD onset and progression. The studies presented in this thesis aimed to better understand and improve upon how DA is assessed in people with AMD.

The first study was a systematic literature review which aimed to evaluate current methodology used to assess DA in people with AMD. Forty-eight eligible studies indicated overwhelming evidence of an association between impaired DA and AMD. Furthermore, there was evidence that the presence of structural abnormalities such as subretinal drusenoid deposits (SDD) are associated with prolongation of DA time. However, data on repeatability and reproducibility of DA measurement was sparse.

In the second study, time-to-event analysis was proposed to be a more statistically powerful method for analysing rod-mediated DA (RMDA) data in people with AMD (n=14) and controls (n=8) (measured by rod-intercept time [RIT; mins] using the AdaptDx [MacuLogix, Hummelstown, PA]). A series of calculations using these data indicated that sample sizes could potentially be reduced by between 40-53% by using the time-to-event analysis compared to a standard t-test of means.

The third study utilised a large multicentre dataset (n=459) from the Northern Ireland Sensory Aging study (NISA). The main aim was to assess differences in RMDA (RIT [mins]; AdaptDx) between different grades of AMD severity classified using a novel OCT-based grading system, compared to the current standard colour fundus photography (CFP) based system (Beckman classification). The second aim was to assess the association between SDD presence and RMDA at different AMD severity grades, using the OCT-based classification. It was concluded RMDA is delayed in eyes with a structural definition of intermediate AMD (iAMD) regardless of whether classified using a CFP or OCT-based criterion when age was correctly controlled for. SDD presence is associated with delays in RMDA within different AMD severity grades.

In the fourth study, data from the large multicentre MACUSTAR cross-sectional study (n=258) was used to assess the test-retest variability and discrimination performance of microperimetry metrics (S-MAIA [CenterVue, Padova, Italy]; mesopic and scotopic average thresholds [MMAT, SMAT; dB]) and RMDA (AdaptDx; RIT [mins]) in eyes with iAMD. MMAT, SMAT and RIT had adequate test-retest variability and are all moderately good at separating people defined as having iAMD from controls under a multi-centre setting (area under the ROC curve was 71% RIT, 68% MMAT and 69% SMAT). More people with iAMD were unable to provide valid AdaptDx data (n=64; 38%) when compared to data yielded from mesopic and scotopic microperimetry (n=39; 23% and n=36; 22%, respectively). Incomplete results and unreliable data using these tests of visual function need to be considered when designing trials using these technologies.

In conclusion, the results of this thesis highlight strengths of using RMDA as a measure of visual function in AMD. Conversely the results indicate some weakness in the current technology used to assess RMDA. Results from the studies presented in this thesis will be useful for those designing new trials where the intention is to use RMDA as a measure of visual function in AMD.

Publication Type: Thesis (Doctoral)
Subjects: R Medicine > RE Ophthalmology
Departments: School of Health & Psychological Sciences > Optometry & Visual Sciences
School of Health & Psychological Sciences > School of Health & Psychological Sciences Doctoral Theses
Doctoral Theses
[thumbnail of Higgins thesis 2023 PDF-A.pdf]
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