Determinants of Test Variability in Scotopic Microperimetry: Effects of Dark Adaptation and Test Indices

AbstractIn age-related macular degeneration (AMD) research, dark adaptation has been found to be a promising functional measurement. In more severe cases of AMD, dark adaptation cannot always be recorded within a maximum allowed time for the test (~ 20–30 min). These data are recorded either as censored data-points (data capped at the maximum test time) or as an estimated recovery time based on the trend observed from the data recorded within the maximum recording time. Therefore, dark adaptation data can have unusual attributes that may not be handled by standard statistical techniques. Here we show time-to-event analysis is a more powerful method for analysis of rod-intercept time data in measuring dark adaptation. For example, at 80% power (at α = 0.05) sample sizes were estimated to be 20 and 61 with uncapped (uncensored) and capped (censored) data using a standard t-test; these values improved to 12 and 38 when using the proposed time-to-event analysis. Our method can accommodate both skewed data and censored data points and offers the advantage of significantly reducing sample sizes when planning studies where this functional test is an outcome measure. The latter is important because designing trials and studies more efficiently equates to newer treatments likely being examined more efficiently.

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Association of Human Plasma Metabolomics with Delayed Dark Adaptation in Age-Related Macular Degeneration

Metabolites ◽

10.3390/metabo11030183 ◽

2021 ◽

Vol 11 (3) ◽

pp. 183

Author(s):

Kevin M Mendez ◽

Janice Kim ◽

Inês Laíns ◽

Archana Nigalye ◽

Raviv Katz ◽

...

Keyword(s):

Amino Acids ◽

Fatty Acid ◽

Macular Degeneration ◽

Dark Adaptation ◽

Ultra Performance Liquid Chromatography ◽

Cross Sectional Study ◽

Age Related Macular Degeneration ◽

Cross Sectional ◽

Age Related ◽

Vitreoretinal Disease

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.

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Intracellular recordings from gecko photoreceptors during light and dark adaptation.

The Journal of General Physiology ◽

10.1085/jgp.66.5.617 ◽

1975 ◽

Vol 66 (5) ◽

pp. 617-648 ◽

Cited By ~ 140

Author(s):

J Kleinschmidt ◽

J E Dowling

Keyword(s):

Membrane Potential ◽

Dark Adaptation ◽

Horizontal Cell ◽

Intracellular Recordings ◽

Receptor Sensitivity ◽

Intensity Curve ◽

Voltage Range ◽

Voltage Change ◽

Sensitivity Change ◽

Compression Treatment

Intracellular recordings were obtained from rods in the Gekko gekko retina and the adaptation characteristics of their responses studied during light and dark adaptation. Steady background illumination induced graded and sustained hyperpolarizing potentials and compressed the incremental voltage range of the receptor. Steady backgrounds also shifted the receptor's voltage-intensity curve along the intensity axis, and bright backgrounds lowered the saturation potential of the receptor. Increment thresholds of single receptors followed Weber's law over a range of about 3.5 log units and then saturated. Most of the receptor sensitivity change in light derived from the shift of the voltage-intensity curve, only little from the voltage compression. Treatment of the eyecup with sodium aspartate at concentrations sufficient to eliminate the beta-wave of the electroretinogram (ERG) abolished initial transients in the receptor response, possibly indicating the removal of horizontal cell feedback. Aspartate treatment, however, did not significantly alter the adaptation characteristics of receptor responses, indicating that they derive from processes intrinsic to the receptors. Dark adaptation after a strongly adapting stimulus was similarly associated with temporary elevation of membrane potential, initial lowering of the saturation potential, and shift of the voltage-intensity curve. Under all conditions of adaptation studied, small amplitude responses were linear with light intensity. Further, there was no unique relation between sensitivity and membrane potential suggesting that receptor sensitivity is controlled at least in part by a step of visual transduction preceding the generation of membrane voltage change.

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