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Scientific Reports Feb 2022Delayed dark adaptation due to impaired rod photoreceptor homeostasis has been reported as the earliest symptom of eye diseases such as age-related macular degeneration,...
Delayed dark adaptation due to impaired rod photoreceptor homeostasis has been reported as the earliest symptom of eye diseases such as age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. Objective measurement of dark adaptation can facilitate early diagnosis to enable prompt intervention to prevent vision loss. However, there is a lack of noninvasive methods capable of spatiotemporal monitoring of photoreceptor changes during dark adaptation. Here we demonstrate functional optical coherence tomography (OCT) for in vivo intrinsic signal optoretinography (ORG) of dark adaptation kinetics in the C57BL/6J mouse retina. Functional OCT revealed a shortening of the outer retina, a rearrangement of the cone and rod photoreceptor interdigitation zone, and a reduction in intrinsic signal amplitude at the photoreceptor inner segment ellipsoid (ISe). A strong positive correlation between the outer retinal shortening and ISe intensity reduction was also confirmed. Functional OCT of dark adaptation kinetics promises an objective method for rapid ORG assessment of physiological integrity of retinal photoreceptors.
Topics: Animals; Blindness; Dark Adaptation; Diabetic Retinopathy; Early Diagnosis; Kinetics; Macular Degeneration; Mice, Inbred C57BL; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa; Tomography, Optical Coherence; Mice
PubMed: 35169239
DOI: 10.1038/s41598-022-06562-4 -
International Journal of Ophthalmology 2015Dark adaptation is a highly sensitive neural function and may be the first symptom of many status including the physiologic and pathologic entity, suggesting that it... (Review)
Review
Dark adaptation is a highly sensitive neural function and may be the first symptom of many status including the physiologic and pathologic entity, suggesting that it could be instrumental for diagnose. However, shortcomings such as the lack of standardized parameters, the long duration of examination, and subjective randomness would substantially impede the use of dark adaptation in clinical work. In this review we summarize the recent research about the dark adaptation, including two visual cycles-canonical and cone-specific visual cycle, affecting factors and the methods for measuring dark adaptation. In the opinions of authors, intensive investigations are needed to be done for the widely use of this significant visual function in clinic.
PubMed: 26682182
DOI: 10.3980/j.issn.2222-3959.2015.06.31 -
Frontiers in Neurology 2018Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary...
Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m and one bright red of 2 log cd/m. The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.
PubMed: 30174642
DOI: 10.3389/fneur.2018.00669 -
Investigative Ophthalmology & Visual... Apr 2023To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia.
PURPOSE
To characterize the association between dark-adapted rod and cone sensitivity and retinal structure in PAX6-related aniridia.
METHODS
Dark-adaptation curves were measured after a 5-minute exposure to bright light with red (625 nm) and green (527 nm) 2° circular light stimuli presented at ≈20° temporal retinal eccentricity in 27 participants with aniridia (nine males; 11-66 years old) and 38 age-matched healthy controls. A two-stage exponential model was fitted to each participant's responses to determine their cone and rod thresholds over time. The thicknesses of macular inner and outer retinal layers were obtained from optical coherence tomography images in 20 patients with aniridia and the 38 healthy controls. Aniridia-associated keratopathy (AAK) grade (0-3) and lens opacities were quantified by clinical examination of the anterior segment.
RESULTS
The rod-cone break time was similar between patients with aniridia and healthy controls. Dark-adapted cone and the rod thresholds were higher in aniridia compared with healthy controls. In aniridia, foveal outer retinal layer thickness correlated with both final cone and rod thresholds. A multiple regression model indicated that foveal outer retinal layer thickness and age were the main explanatory variables to predict both final cone and rod thresholds in aniridia when the AAK grade was 2 or less.
CONCLUSIONS
The results show that both rod- and cone-related functions are affected in PAX6-related aniridia and suggest that retinal anatomical and physiological changes extend beyond the area commonly studied in this condition: the central macula.
Topics: Male; Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Dark Adaptation; Retina; Retinal Cone Photoreceptor Cells; Photoreceptor Cells, Vertebrate; Vision Disorders; Corneal Diseases; Aniridia; Tomography, Optical Coherence
PubMed: 37067366
DOI: 10.1167/iovs.64.4.18 -
Survey of Ophthalmology 2021Diabetic retinal disease remains a leading cause of vision loss despite currently available screening methods, ocular treatments, and efforts to control metabolic... (Review)
Review
Diabetic retinal disease remains a leading cause of vision loss despite currently available screening methods, ocular treatments, and efforts to control metabolic dysfunction. It is now understood that diabetes damages the entire retina and the cellular components of the neurovascular unit. Multiple studies have demonstrated impairment of various aspects of retinal function across the spectrum of retinopathy severity. Here we review these tests, the principles underlying their use, clinical data from multiple publications, the strengths and limitations of the studies, and prospects for their application to understand the pathophysiology of diabetic retinal disease and monitor its response to therapy. We focus on visual acuity, contrast sensitivity, color vision, visual field, and dark adaptation and their use to understand the pathophysiology of diabetic retinopathy and as potential endpoints for clinical trials.
Topics: Dark Adaptation; Diabetes Mellitus; Diabetic Retinopathy; Humans; Retina; Visual Acuity; Visual Fields
PubMed: 32866468
DOI: 10.1016/j.survophthal.2020.08.003 -
The Journal of Physiology Nov 2022
Topics: Retinal Rod Photoreceptor Cells; Retinal Cone Photoreceptor Cells; Electroretinography; Retina; Dark Adaptation
PubMed: 36083438
DOI: 10.1113/JP283652 -
Progress in Retinal and Eye Research May 2017This article discusses retinal oxygenation and retinal metabolism by focusing on measurements made with two of the principal methods used to study O in the retina:... (Review)
Review
This article discusses retinal oxygenation and retinal metabolism by focusing on measurements made with two of the principal methods used to study O in the retina: measurements of PO with oxygen-sensitive microelectrodes in vivo in animals with a retinal circulation similar to that of humans, and oximetry, which can be used non-invasively in both animals and humans to measure O concentration in retinal vessels. Microelectrodes uniquely have high spatial resolution, allowing the mapping of PO in detail, and when combined with mathematical models of diffusion and consumption, they provide information about retinal metabolism. Mathematical models, grounded in experiments, can also be used to simulate situations that are not amenable to experimental study. New methods of oximetry, particularly photoacoustic ophthalmoscopy and visible light optical coherence tomography, provide depth-resolved methods that can separate signals from blood vessels and surrounding tissues, and can be combined with blood flow measures to determine metabolic rate. We discuss the effects on retinal oxygenation of illumination, hypoxia and hyperoxia, and describe retinal oxygenation in diabetes, retinal detachment, arterial occlusion, and macular degeneration. We explain how the metabolic measurements obtained from microelectrodes and imaging are different, and how they need to be brought together in the future. Finally, we argue for revisiting the clinical use of hyperoxia in ophthalmology, particularly in retinal arterial occlusions and retinal detachment, based on animal research and diffusion theory.
Topics: Animals; Dark Adaptation; Humans; Oxygen; Regional Blood Flow; Retina; Retinal Diseases
PubMed: 28109737
DOI: 10.1016/j.preteyeres.2017.01.003 -
Investigative Ophthalmology & Visual... Mar 2024A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and... (Review)
Review
A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.
Topics: Humans; Adult; Aged; Macular Degeneration; Retina; Macula Lutea; Geographic Atrophy; Retinal Cone Photoreceptor Cells
PubMed: 38466281
DOI: 10.1167/iovs.65.3.4 -
Eye (London, England) Feb 2016Visual function improves with oxygen inhalation in people with diabetes even in the absence of visible retinopathy. Rods consume the most oxygen in the retina due to the... (Review)
Review
Visual function improves with oxygen inhalation in people with diabetes even in the absence of visible retinopathy. Rods consume the most oxygen in the retina due to the high metabolic activity required to maintain the dark current. Therefore, Arden hypothesized that in diabetes where oxygen supply may also be affected due to the changes in retinal vasculature, prevention of dark adaptation may be a viable option to prevent or decrease the rate of progression of diabetic retinopathy. Animal experiments have proven that the absence of rods decreases the development of retinal neovascularisation. The same principle applies to panretinal photocoagulation, an established treatment for proliferative diabetic retinopathy. Recently, a few clinical studies have also shown that preventing dark adaptation by suppressing rods with 500-nm light source at night decreases the rate of progression of early diabetic retinopathy and maculopathy in the short-term. We await the results of a large two-year multi-centre trial (CLEOPATRA trial) to evaluate the long-term effects of decreasing dark adaptation by applying a 500nm light source as a mask over eyes with non-central diabetic macular oedema.
Topics: Animals; Dark Adaptation; Diabetic Retinopathy; Humans; Hypoxia; Light; Oxygen; Oxygen Consumption; Retina; Retinal Rod Photoreceptor Cells
PubMed: 26656085
DOI: 10.1038/eye.2015.254 -
Current Eye Research May 2023Studies on age-related macular degeneration often use rod-mediated dark adaptation (RMDA) to evaluate macular functional health, studying eyes with cataract and...
PURPOSE
Studies on age-related macular degeneration often use rod-mediated dark adaptation (RMDA) to evaluate macular functional health, studying eyes with cataract and pseudophakic eyes within the same sample. We examine a poorly understood issue-whether rod intercept time (RIT), a measure of RMDA, changes after cataract surgery and intraocular lens (IOL) insertion as compared to RIT before cataract surgery. Cataract may serve as a filter reducing photo-bleach magnitude prior to surgery, biasing RMDA interpretation.
METHODS
A pre-/post-cataract surgery design was used. Persons with nuclear sclerotic and/or cortical cataract per the electronic health record were enrolled. Prior to cataract surgery, visual acuity, RMDA, and the LOCS III classification documenting cataract presence/severity were measured. Thirty days after surgery (mean), visual acuity and RMDA were repeated, followed by fundus photos to document macular health.
RESULTS
Twenty-four participants (mean age 72.7 years, standard deviation 5.6) enrolled. All eyes had nuclear sclerotic and nuclear color cataract; 68% had cortical cataract. All IOLs were monofocal with 21 having blue blocking characteristics and 3 had clear IOLs. Most eyes had higher RIT post-surgery (15.6 min, SD 6.7) as compared to pre-surgery (13.7 min, SD 6.4), = 0.0006, meaning that RMDA was slower post-surgery. Eyes with moderate cataract (<4 on any LOCS III grade) had RIT that increased on average by 0.7 min; those with more advanced cataract (≥4) had RIT that increased by 3.1 min ( = 0.0116). Results were unchanged when clear IOLs were removed from analysis.
CONCLUSION
RMDA was significantly slower (RIT was greater) following cataract surgery, with the greatest impact on RIT in older eyes after surgery for more advanced cataract. These findings suggest that persons with more advanced cataract may bias results when evaluating RMDA using RIT.
Topics: Humans; Aged; Dark Adaptation; Cataract Extraction; Capsule Opacification; Visual Acuity; Cataract
PubMed: 36662498
DOI: 10.1080/02713683.2023.2171438