Relationship between Clinical Macular Changes and Retinal Function in Age-Related Macular Degeneration

Dimitrov, Peter; Robman, Liubov; Varsamidis, Mary; Aung, Khin Zaw; Makeyeva, Galina; Busija, Ljoudmila; Vingrys, Algis J.; Guymer, Robyn H.

doi:10.1167/iovs.11-8958

Cited by 51 publications

(67 citation statements)

References 40 publications

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“…However, we did not always find a reduction in sensitivity when clinical fundus signs, such as the addition of pigmentary disturbance or in the presence of GA, were seen in the fellow eye, indicating a higher clinical risk for progression. Consistent with our earlier reports using other functional modalities, 14 we found that the group with drusen 63 to 125 lm in size had most variation in sensitivity in the inner rings, in both test modalities, suggesting that at this stage of AMD some people will have normal function while others will have quite abnormal results. Perhaps at this stage we might be able to differentiate those destined to have progression and those less likely to do so.…”

Section: Discussionsupporting

confidence: 91%

Static and Flicker Perimetry in Age-Related Macular Degeneration

Luu

Dimitrov

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Luu CD, Dimitrov PN, Wu Z, et al. Static and flicker perimetry in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013;54:3560-3568. DOI:10.1167/ iovs.12-10465 PURPOSE. The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry.METHODS. This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. CONCLUSIONS. Static and flicker perimetry were affected similarly across the spectrum of AMD severity, and methods appeared to be valid techniques for assessing retinal sensitivity in AMD once drusen > 125 lm are present, but before the development of late AMD.

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Section: Discussionsupporting

confidence: 91%

Static and Flicker Perimetry in Age-Related Macular Degeneration

Luu

Dimitrov

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…5, 14, 46, 49 Further investigation of this issue is merited, especially in light of a recent study suggesting that 14 Hz flicker and blue color thresholds have good diagnostic sensitivity and ease of test administration. 20 Rod-mediated dark adaptation was assessed in one eye only, unlike the other visual function tests measured in both eyes; however, even with the reduced sample size, there was adequate statistical power to demonstrate significant differences in rod-intercept between the two groups. In addition, the pattern of results was unchanged when analyses were restricted to eyes for which dark adaptation was measured.…”

Section: Discussionmentioning

confidence: 99%

“…These include spatial contrast sensitivity, visual acuity under low luminance and/or low contrast, photopic and scotopic light sensitivity, flicker sensitivity, and dark adaptation. 4–20 The purpose of this study was to assess several visual functional measures in eyes in normal macular health and eyes in the very earliest stages of AMD. Our goal is to understand which aspects of visual function are significantly impacted in the initial stages of the disease.…”

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confidence: 99%

Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health

Owsley

Huisingh

Clark

et al. 2015

Current Eye Research

103

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Purpose To compare the ability of several visual functional tests in terms of the strength of their associations with the earliest phases of age-related macular degeneration (AMD), which bears on their potential to serve as functional endpoints in evaluating treatments for early AMD and prevention strategies. Materials and Methods Eyes from adults ≥ 60 years old were identified as being in normal macular health or in the earliest stages of AMD (steps 2, 3 or 4) through grading of color stereo-fundus photos by an experienced grader masked to all other study variables who used the 9-step Age-Related Eye Disease Study (AREDS) classification system for AMD severity. Visual function was assessed using the following tests: best-corrected visual acuity, low luminance visual acuity, spatial contrast sensitivity, macular cone-mediated light sensitivity, and rod-mediated dark adaptation. Results A total of 1,260 eyes were tested from 640 participants; 1,007 eyes were in normal macular health (defined as step 1 in AREDS system) and 253 eyes had early AMD (defined as step 2, 3, or 4). Adjusting for age and gender, early AMD eyes had 2 times the odds of having delayed rod-mediated dark adaptation than eyes in normal macular health (p = 0.0019). Visual acuity, low luminance acuity, spatial contrast sensitivity, and macular light sensitivity did not differ between normal eyes and early AMD eyes. Conclusions Eyes in the earliest phases of AMD were two times more likely to have delayed rod-mediated dark adaptation, as assessed by the rod-intercept, as compared to older eyes in normal macular health, whereas there was no difference in early AMD versus normal eyes in tests of visual acuity, low luminance acuity, macular light sensitivity, and spatial contrast sensitivity.

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“…Because an optimal therapeutic intervention would target early stages of disease, there is a great need for safe and effective ways to detect AMD early and safely monitor its progression. Decline in visual functions, particularly dark adaptation, becomes yet another potential biomarker in monitoring/predicting pathologies leading to AMD (22)(23)(24). Although development of a large number of animal models has helped to advance our understanding of retinal pathobiology and identify specific genetic factors that contribute to photoreceptor degeneration, inflammation, and the biochemistry of many retinal processes, these models all have limitations (25)(26)(27)(28).…”

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Serum levels of lipid metabolites in age‐related macular degeneration

et al. 2015

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Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4 2/2 Rdh8 2/2 mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decreased as compared with the eyes of control dark-adapted C57BL/6J mice. In addition, exposure to intense light correlated with higher levels of prostaglandin G2 in the eyes of Abca4 2/2 Rdh8 2/2 mice. Intense light exposure also lowered DHA levels in the eyes of wild-type C57BL/6J mice without discernible retinal degeneration. Analysis of human serum from patients with AMD recapitulated these dysregulated DHA levels and revealed dysregulation of arachidonic acid (AA) levels as well (∼32% increase in patients with AMD compared with average levels in healthy individuals). From these observations, we then built a statistical model that included levels of DHA and AA from human serum. This model had a 74% probability of correctly identifying patients with AMD from controls. Addition of a genetic analysis for one of the most prevalent amino acid substitutions in the age-related maculopathy susceptibility 2 gene linked to AMD, Ala 69 →Ser, did not improve the statistical model. Thus, we have characterized a reliable method with the potential to detect AMD without a genetic component, paving the way for a larger-scale clinical evaluation. Our studies on mouse models along with the analysis of human serum suggest that our small molecule-based model may serve as an effective tool to estimate the risk of developing AMD.-Orban, T., Johnson, W. M., Dong, Z., Maeda, T., Maeda, A., Sakai, T., Tsuneoka, H., Mieyal, J. J., Palczewski, K. Serum levels of lipid metabolites in age-related macular degeneration. FASEB J. 29, 4579-4588 (2015). www.fasebj.org

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Relationship between Clinical Macular Changes and Retinal Function in Age-Related Macular Degeneration

Abstract: Steady state thresholds (F14Hz and BCT) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes. This suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.

Cited by 51 publications

References 40 publications

Static and Flicker Perimetry in Age-Related Macular Degeneration

Static and Flicker Perimetry in Age-Related Macular Degeneration

Comparison of Visual Function in Older Eyes in the Earliest Stages of Age-related Macular Degeneration to Those in Normal Macular Health

Serum levels of lipid metabolites in age‐related macular degeneration

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