Peripheral Changes Associated With Delayed Dark Adaptation in Age-related Macular Degeneration

Park, Dong Ho; Mukai, Ryo; Silverman, Rebecca; Oellers, Patrick; Mach, Steven; Kim, Ivana K.; Vavvas, Demetrios G.; Miller, Joan W.; Husain, Deeba

doi:10.1016/j.ajo.2018.03.035

Cited by 16 publications

(17 citation statements)

References 34 publications

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“…To analyze the association between plasma metabolite levels and dark adaptation, we used multilevel mixed-effects linear model through the R package "lme4" [72], accounting for the inclusion of two dark adaptation measures (i.e., left eye and right eye) and a single measure of plasma metabolite levels for each patient [2,4,9]. In these models, the outcome was RIT.…”

Section: Discussionmentioning

confidence: 99%

“…Other functional outcome measures have been proposed, such as contrast sensitivity, low-luminance visual acuity, photopic or scotopic light sensitivity, and dark adaptation (DA) [2,3]. DA, in particular, is promising as even in the setting of normal visual acuity, patients with early stages of the disease often report loss of night vision and reduced ability to adapt from brightly lit to dark environments [4]. Studies have shown that with the use of a commercially available device-the AdaptDx (MacuLogix, Harrisburg, PA, USA) dark adaptometer-dark adaptation can differentiate between patients with and without AMD, and across severity stages of the disease [2,3,5,6].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…The entire retina is affected in retinitis pigmentosa [3]. Recent studies suggest that AMD patients have peripheral retinal changes including drusen accumulation and pigment changes associated with delayed dark adaptation [49, 50], emphasizing the need to deliver the therapeutics to the entire retina in these diseases. Our data suggest that the novel suprachoroidal IO/HSA NPs injection may present a promising intraocular drug delivery approach to achieve distribution of the treatment throughout the posterior segment by a single injection with prolonged intraocular residence.…”

Section: Discussionmentioning

confidence: 99%

In vivo MRI assessment of bioactive magnetic iron oxide/human serum albumin nanoparticle delivery into the posterior segment of the eye in a rat model of retinal degeneration

et al. 2019

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BackgroundRetinal degeneration diseases affect millions of patients worldwide and lead to incurable vision loss. These diseases are caused by pathologies in the retina and underlying choroid, located in the back of the eye. One of the major challenges in the development of treatments for these blinding diseases is the safe and efficient delivery of therapeutics into the back of the eye. Previous studies demonstrated that narrow size distribution core–shell near infra-red fluorescent iron oxide (IO) nanoparticles (NPs) coated with human serum albumin (HSA, IO/HSA NPs) increase the half-life of conjugated therapeutic factors, suggesting they may be used for sustained release of therapeutics. In the present study, the in vivo tracking by MRI and the long term safety of IO/HSA NPs delivery into the suprachoroid of a rat model of retinal degeneration were assessed.ResultsTwenty-five Royal College of Surgeons (RCS) pigmented rats received suprachoroidal injection of 20-nm IO/HSA NPs into the right eye. The left eye was not injected and used as control. Animals were examined by magnetic resonance imaging (MRI), electroretinogram (ERG) and histology up to 30 weeks following injection. IO/HSA NPs were detected in the back part of the rats’ eyes up to 30 weeks following injection by MRI, and up to 6 weeks by histology. No significant differences in retinal structure and function were observed between injected and non-injected eyes. There was no significant difference in the weight of IO/HSA NP-injected animals compared to non-injected rats.ConclusionsMRI could track the nanoparticles in the posterior segment of the injected eyes demonstrating their long-term persistence, and highlighting the possible use of MRI for translational studies in animals and in future clinical studies. Suprachoroidal injection of IO/HSA NPs showed no sign of adverse effects on retinal structure and function in a rat model of retinal degeneration, suggesting that suprachoroidal delivery of IO/HSA NPs is safe and that these NPs may be used in future translational and clinical studies for extended release drug delivery at the back of the eye.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0438-y) contains supplementary material, which is available to authorized users.

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“…Chen et al [36] described a key association between SDD presence and accelerated worsening of DA in their longitudinal study. Conversely, peripheral classic drusen (both presence and number) have not been found to be associated with slowed RIT [25].…”

Section: Adaptdx: Relationship With Other Measuresmentioning

confidence: 82%

“…Others have reported an association between impaired DA and changes in choroidal thickness [23], changes in retinal thickness (adjusted for age and VA) [37], reticular pigmentary changes and presence of a mottled decreased fundus autofluorescence (FAF) pattern in the midperipheral zone [25]. Laíns et al [24] found that structural abnormalities (such as classic drusen, ellipsoid zone disruption and serous pigment epithelium detachment) affected DA when found in the testing location, even after controlling for AMD stage and age.…”

Section: Adaptdx: Relationship With Other Measuresmentioning

confidence: 99%

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

et al. 2021

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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.

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Peripheral Changes Associated With Delayed Dark Adaptation in Age-related Macular Degeneration

Cited by 16 publications

References 34 publications

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

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

In vivo MRI assessment of bioactive magnetic iron oxide/human serum albumin nanoparticle delivery into the posterior segment of the eye in a rat model of retinal degeneration

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

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