Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration.
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ABSTRACT:
SUBMITTER: Grewal MK
PROVIDER: S-EPMC8121851 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose:Functional studies of rods in age-related macular degeneration using the Medmont Dark-Adapted Chromatic Perimeter (DACP) have demonstrated impairments in scotopic sensitivities and dark adaptation (DA). We investigated the intersession repeatability of scotopic sensitivity and DA parameters including the rod intercept time recorded from the Medmont DACP. Methods:Scotopic thresholds (14 test points) and DA using a 30% photobleach (eight test points) were measured on two separate days from participants 50 years of age or older with a range of age-related macular degeneration severity at loci superior and inferior to the fovea. Repeatability coefficients were calculated for prebleach scotopic sensitivity, and for DA parameters including rod intercept time. Results:Twelve participants (mean age, 79.7 ± 8.1 years) repeated Medmont DACP testing within 50 days. Repeatability coefficients for prebleach scotopic sensitivity to long wavelength (red, 625 nm) and short wavelength (cyan, 505 nm) were 5.9 dB and 7.2 dB, respectively. The DA curve-derived repeatability coefficients for cone threshold was 3.9 dB, final threshold 5.3 dB, with an R value of 0.075 decades/min, rod intercept time 7.6 minutes, and RITslope 0.54 min/degree. Conclusions:This study establishes repeatability coefficients for scotopic thresholds and multiple DA parameters obtained with the Medmont DACP in patients with age-related macular degeneration. These repeatability coefficients will serve as the basis for determining clinically meaningful change in rod function in future clinical trials. Translational Relevance:Measures of repeatability parameters of scotopic thresholds and DA are essential to the accurate interpretation of results in future studies and trials using these measures.
| S-EPMC7414623 | biostudies-literature
Project description:Although rod photoreceptors are initially affected in retinitis pigmentosa (RP), the full-field of rod vision is not routinely characterized due to the unavailability of commercial devices detecting rod sensitivity. The purpose of this study was to quantify rod-mediated vision in the peripheral field from patients with RP using a new commercially available perimeter.Participants had one eye dilated and dark-adapted for 45 minutes. A dark-adapted chromatic (DAC) perimeter tested 80 loci 144° horizontally and 72° vertically with cyan stimuli. The number of rod-mediated loci (RML) were analyzed based on normal cone sensitivity (method 1) and associated with full-field electroretinography (ERG) responses by Pearson's r correlation and linear regression. In a second cohort of patients with RP, RML were identified by two-color perimetry (cyan and red; method 2). The two methods for ascribing rod function were compared by Bland-Altman analysis.Method 1 RML were correlated with responses to the 0.01 cd.s/m2 flash (P < 0.001), while total sensitivity to the cyan stimulus showed correlation with responses to the 3.0 cd.s/m2 flash (P < 0.0001). Method 2 detected a mean of 10 additional RML compared to method 1.Scotopic fields measured with the DAC detected rod sensitivity across the full visual field, even in some patients who had nondetectable rod ERGs. Two-color perimetry is warranted when sensitivity to the cyan stimulus is reduced to ≤20 dB to get a true estimation of rod function.Many genetic forms of retinitis pigmentosa (RP) are caused by mutations in rod-specific genes. However, treatment trials for patients with RP have relied primarily on photopic (cone-mediated) tests as outcome measures because there are a limited number of available testing methods designed to evaluate rod function. Thus, efficient methods for quantifying rod-mediated vision are needed for the rapidly increasing numbers of clinical trials.
| S-EPMC5549985 | biostudies-other
Project description:PurposeTo determine the retest variability of mesopic and two-color dark-adapted (DA) fundus-controlled perimetry (FCP), to evaluate the predictive value of patient reliability indices, and to analyze the extent of impairment of rod- and cone function in neovascular age-related macular degeneration (nAMD).MethodsA total of 50 eyes of 50 patients with nAMD (mean age, 76.1 years) and 70 eyes of 70 age-similar normal subjects underwent multimodal imaging as well as mesopic and DA two-color perimetry using the S-MAIA device. A subset of patients (n = 28) underwent duplicate testing for retest reliability assessment. Mixed models were used for analysis of the hierarchical data.ResultsIn eyes with nAMD, the coefficient of repeatability was (mean ± standard deviation [SD]) 5.99 ± 1.55 dB for mesopic, 6.14 ± 2.19 dB for DA cyan, and 6.06 ± 1.09 dB for DA red testing. "Patient reliability indices" explained 55%, 54.2%, and 64.2% of the variance in retest variability. The mean sensitivity loss was greater for DA cyan compared to DA red testing (cyan-red differences [mean ± SD] -2.63 ± 3.87 dB, P < 0.001).ConclusionsThe relatively greater degree of DA cyan versus DA red sensitivity loss indicates preferential rod vulnerability in nAMD, and qualifies rod function-based outcomes measures as potential sensitive and early markers of treatment response in nAMD.Translational relevanceThe S-MAIA allows reliable testing of mesopic, DA cyan, and DA red sensitivity in patients with nAMD. Patient reliability indices may serve as eligibility criteria for clinical trials to identify patients with adequate retest reliability.
| S-EPMC6327348 | biostudies-literature
Project description:PurposeIn choroideremia (CHM) carriers, scotopic sensitivity was assessed by dark adapted chromatic perimetry (DACP) and outer retinal structure was evaluated by multimodal imaging.MethodsNine carriers (18 eyes) and 13 healthy controls (13 eyes) underwent DACP testing with cyan and red stimuli. Analysis addressed peripapillary (4 test locations closest to the optic disc), macular (52 locations), and peripheral (60 locations outside the macula) regions. Responses were considered to be rod-mediated when cyan relative to red sensitivity was >5 dB. Fundus imaging included spectral domain optical coherence tomography (SD-OCT), short-wavelength (SW-AF), near-infrared (NIR-AF), ultrawide-field (200 degrees) pseudocolor fundus imaging, and quantitative (qAF) fundus autofluorescence.ResultsDetection of the cyan stimulus was rod mediated in essentially all test locations (99.7%). In the macular and peripheral areas, DACP sensitivity values were not significantly different from healthy eyes. In the peripapillary area, sensitivities were significantly decreased (P < 0.05). SD-OCT imaging ranged from hyper-reflective lesions and discontinuities of the outer retinal bands to hypertransmission of signal. SW-AF and NIR-AF images presented with peripapillary atrophy in seven patients (14 eyes). Mosaicism was detectable in SW-AF images in seven patients and in NIR-AF images in five patients. Frank hypo-autofluorescence was visible in eight patients with distinct chorioretinopathy in seven patients. The qAF values were below the 95% confidence interval (CI) of healthy age-matched individuals in 12 eyes.ConclusionsRod mediated scotopic sensitivity was comparable to that in control eyes in macular and peripheral areas but was decreased in the peripapillary area where changes in retinal structure were also most severe.
| S-EPMC9284471 | biostudies-literature
Project description:PURPOSE:To examine the feasibility and utility of dark-adapted two-color fundus-controlled perimetry (FCP) in patients with cuticular, reticular, and soft drusen, and to compare FCP data to microstructural spectral-domain optical coherence tomography (SD-OCT) data. METHODS:Forty-four eyes (24 eyes of 24 patients with drusen, age 69.4?±?12.6 years; 20 normal eyes of 16 subjects, 61.7?±?12.4 years) underwent duplicate mesopic, dark-adapted cyan and dark-adapted red FCP within 14° of the central retina (total of 12?936 threshold tests) using the Scotopic Macular Integrity Assessment (S-MAIA, CenterVue, Padova, Italy) device. FCP data were registered to SD-OCT data to obtain outer nuclear layer, inner and outer photoreceptor segment, and retinal pigment epithelium drusen complex (RPEDC) thickness data spatially corresponding to the stimulus location and area (0.43°). Structure-function correlations were assessed using mixed-effects models. RESULTS:Mean deviation values for eyes with cuticular, soft, and reticular drusen were similar for mesopic (-2.1, -3.4, and -3.6?dB) and dark-adapted red (-1.4, -2.6, and -3.3?dB) FCP. For the dark-adapted cyan FCP (0.1, -1.9, and -5.0?dB) and for the cyan-red sensitivity difference (+1.0, +0.5, and -2.4?dB), the mean deviation values differed significantly in dependence of the predominant drusen type (one-way ANOVA; p?<?0.05). RPEDC thickness was associated with reduction of mesopic sensitivity (-0.34?dB/10?µm RPEDC thickening; p?<?0.001), dark-adapted cyan sensitivity (-0.11?dB/10?µm RPEDC thickening; p?=?0.003), and dark-adapted red sensitivity (-0.26?dB/10?µm RPEDC thickening; p?<?0.001). CONCLUSIONS:In contrast to mesopic FCP, dark-adapted two-color FCP allowed for meaningful differential testing of rod and cone function in patients with drusen indicating predominant cone dysfunction in eyes with cuticular drusen and predominant rod dysfunction in eyes with reticular drusen. RPEDC thickness was the strongest predictor of the evaluated SD-OCT biomarkers for point-wise sensitivity.
| S-EPMC6292882 | biostudies-literature
Project description:PurposeThe purpose of this study was to investigate scotopic contour deformation detection (sCDD), and its structural determinants, in participants with intermediate age-related macular degeneration (iAMD) with or without reticular pseudodrusen (RPD).MethodsForty-one participants (aged 58-89 years), including 9 with iAMD and RPD, 16 with iAMD only, and 16 controls, underwent functional testing. The sCDD was evaluated with radial frequency arcs presented at 4 loci: ±4 degrees and 8 degrees vertical eccentricity. Scotopic thresholds and dark adaptation (DA) were measured at the same loci. Retinal layers of spectral domain optical coherence tomography (SD-OCT) volume scans were segmented. To establish the concurrent validity of the functional test, we evaluated the fraction of variability in sCDD thresholds explained by SD-OCT data.ResultsThe iAMD group had significantly worse sCDD thresholds compared with controls (8 degrees inferior retina: P = 0.004 and the 4 degrees loci: P < 0.02 for both). Elevated sCDD thresholds were observed in iAMD and RPD eyes at loci with normal scotopic thresholds; the opposite was rarely encountered. Elevated sCDD thresholds were also observed in iAMD eyes with normal DA. Elevated sCDD thresholds were associated with increased age and presence of late AMD in the fellow eye. The optimal machine learning model predicted 16% of variability (cross-validated R2) in sCDD thresholds at 8 degrees.DiscussionA novel scotopic contour deformation task can provide unique information about rod dysfunction in participants with iAMD and RPD not observed with structural and other functional assessments. Rod dysfunction observed with scotopic contour deformation testing was associated with factors linked to risk of AMD progression.
| S-EPMC9234356 | biostudies-literature
Project description:Age-related macular degeneration has a strong epidemiological association with cardiovascular disease. One pathogenic hypothesis that applies to both diseases is the concept of an abnormal cellular response to injury resulting in a disease phenotype. It has been hypothesized that this phenotype is also present in dermal fibroblasts. This study tests this hypothesis by examination of the expression profiles of fibroblasts obtained from diseased patients and subjected to sublethal cell injury. Keywords: other
2004-09-02 | GSE1719 | GEO
Project description:Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.
| S-EPMC3830684 | biostudies-literature
Project description:Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. The purpose of this experiment was to characterize the transcriptomic changes associated with macrophage aging.
2018-07-15 | GSE111382 | GEO
Project description:PurposeTo compare per-region macular sensitivity and delay from objective perimetry with Matrix perimetry and retinal thickness in mild diabetic macular edema (DMO).MethodsThirty-three patients with type 2 diabetes (T2D) aged 59.2 ± 10.5 years participated in a longitudinal study. Macular thickness, sensitivities and delays from the objectiveFIELD Analyzer (OFA), and Matrix perimeter sensitivities were mapped onto a common spatial layout to compute per-region correlations between structure/function measures. A generalized linear mixed-effects logistic regression model determined which variables contributed to clinical diagnosis of DMO.ResultsFor OFA, the mean sensitivity differences compared with normal in patients with T2D were negative and the mean delay differences positive, indicating lowered sensitivities and prolonged delays, both increasing with diabetes duration. Shorter diabetes duration could produce either localized peripheral hypersensitivities or shorter delays. Functional change could occur when retinal thickness was stable. Peripheral macular thickness correlated with central and peripheral OFA sensitivity and delay, all P < 0.0012 in DMO and a median of P = 0.001 without DMO; this was not true for Matrix sensitivities. The logistic model determined that peripheral thickness, OFA sensitivity (P = 0.043), and time in the study (P = 0.001) contribute independently to the odds of DMO versus no DMO.ConclusionsMean sensitivities decreased and mean delays increased with duration of diabetes. Peripheral macular thickness correlated significantly with central and peripheral macular OFA sensitivity and delay. Peripheral macular thickness and functional measures may provide sensitive prognostic data.Translational relevanceFunctional loss can precede structural change in DMO, so including such functional assessment for deciding on treatment may be beneficial.
| S-EPMC8631055 | biostudies-literature