Disclosing disease mechanisms with a spatio-temporal summation paradigm

Zele, Andrew J.; O’Loughlin, Rebecca K.; Guymer, Robyn H.; Vingrys, Algis J.

doi:10.1007/s00417-005-0121-5

Cited by 19 publications

(25 citation statements)

References 39 publications

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“…It is still not clear whether functional deficits in early ARM measured with various psychophysical tests are primarily caused by reduced sensitivity of photoreceptors, [20][21][22][23] by postreceptoral damage 21,24,25 or by damage to other tissues involved in ARM such as the RPE/Bruch's membrane complex 10,11,26 or the choroid. [27][28][29][30][31] Knowledge of the primary retinal site affected by ARM would be helpful in targeting the application of future treatments, such as pharmaceuticals, retinal transplants, or computer chips.…”

Section: Introductionmentioning

confidence: 99%

Functional loss in early age-related maculopathy: the ischaemia postreceptoral hypothesis

Feigl

Brown

Lovie‐Kitchin

et al. 2006

Eye

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We review proposed models and psychophysical and electrophysiological tests performed in many studies for early agerelated maculopathy (ARM). We suggest that ischaemia is the trigger for impaired retinal pigment epithelium function causing imbalance of secretion of vascular growth factors, reduced disc degradation capability and reduced metabolic activity and possible inflammatory response. This results in increased deposition of cell debris, such as drusen and thickens Bruch's membrane causing even more ischaemia of the overlying neurosensory retina. The photoreceptors are more resistant to ischaemia given their proximity to the choroid. Furthermore, being 'upstream' from the inner retinal layers, they act as an oxygen sink depriving retinal layers further from the choroid. Postreceptoral cell layers and especially parts of the inner nuclear layer that are located in the watershed zone between two sources of blood supply are preferentially vulnerable to ischaemia. Based on psychophysical and electrophysiological findings we propose that most of the function impairment in early ARM starts postreceptorally.

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Section: Introductionmentioning

confidence: 99%

Functional loss in early age-related maculopathy: the ischaemia postreceptoral hypothesis

Feigl

Brown

Lovie‐Kitchin

et al. 2006

Eye

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“…The good fit of our data to a slope of 0.5 indicates that the function is noise limited by a postreceptoral detector. 34 Furthermore, sampling has occurred through a single detector, rather than recruiting multiple detectors which should give a slope of 0.25. 34 It follows that, given the critical area of the stimulus on the retina (achromatic, 0.025 mm 2 ; and S-cone, 0.035 mm 2 ) and the much smaller extent of ganglion cell receptive fields in the foveal region, 40 the detector in question must invoke higher-order (extraretinal) visual processes.…”

Section: Discussionmentioning

confidence: 99%

“…34 Furthermore, sampling has occurred through a single detector, rather than recruiting multiple detectors which should give a slope of 0.25. 34 It follows that, given the critical area of the stimulus on the retina (achromatic, 0.025 mm 2 ; and S-cone, 0.035 mm 2 ) and the much smaller extent of ganglion cell receptive fields in the foveal region, 40 the detector in question must invoke higher-order (extraretinal) visual processes. Significant decreases in sensitivity were demonstrated in highly myopic eyes, both at partial and maximum summation, to achromatic and S-cone-isolating stimuli, demonstrating a loss of sensitivity in both the luminance and S-cone systems.…”

Section: Discussionmentioning

confidence: 99%

“…A two-component model was fit to each participant's thresholds. 34 Spatial Contrast Sensitivity. Achromatic contrast detection thresholds were determined for contrast-modulated (Michelson contrast), horizontal, sinusoidal luminance gratings of six spatial frequencies (0.5-9.7 cyc/deg).…”

Section: Psychophysical Testingmentioning

confidence: 99%

“…Spatial summation was determined by using six spot sizes ranging from 0.2°to 5.4°diameter, using previously reported methodology. 34 In brief, spot sizes were chosen to span the critical area, which is given by the transition from noise-limited processes (slope, 0.5) to complete summation (slope, 0). A two-component model was fit to each participant's thresholds.…”

Section: Psychophysical Testingmentioning

confidence: 99%

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Altered Visual Sensitivity in Axial High Myopia: A Local Postreceptoral Phenomenon?

Jaworski¹,

Gentle²,

Zele³

et al. 2006

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The present study investigated retinal integrity in high myopia using spatial psychophysical tasks. METHODS. Ten axial high myopes (Ϫ8.5 to Ϫ11.5 D) and 10 age-matched control subjects (Ϯ1.0 D) were recruited. All participants underwent clinical examination and ocular biometry and demonstrated no visible macular disease with visual acuities better than 6/12. Foveal summation thresholds were determined for white and S-cone-isolating spots of various diameters up to 5.4°and spatial contrast sensitivity to luminance sine wave gratings (0.5-9.7 cyc/deg). Data were analyzed after correction for the magnification induced by eye size and correcting lens power. RESULTS. Spatial summation for both white and S-cone-isolating spots showed a generalized loss of sensitivity at all spot sizes in myopes relative to control subjects (P ϭ 0.01). Critical areas at maximum summation were significantly larger in myopes, for S-cone isolating spots only, after image size correction (P ϭ 0.048). Sensitivity at maximum summation correlated negatively with vitreous chamber depth for both targets (P ϭ 0.005). Sensitivities for S-cone and luminance spots also correlated (P Ͻ 0.001), indicating widespread dysfunction. Myopes displayed contrast sensitivity losses at high spatial frequencies (P Յ 0.006) with a normal peak contrast sensitivity. CONCLUSIONS. These data can be interpreted to indicate that highly myopic eyes have either (1) a reduction in the number of receptors and/or a reduction in their sensitivity or, (2) a reduction in the sensitivity of postreceptoral processes. The presence of normal contrast sensitivity at low spatial frequencies indicates dysfunction at a postreceptoral level in high myopes. (Invest Ophthalmol Vis Sci. 2006;47:3695-3702) M yopia is a common refractive condition, which occurs due to an excessive axial enlargement of the eye that is not coordinated with the power of the eye's optical surfaces. The resultant visual image of distant objects is formed in front of the photoreceptor plane. This excessive axial enlargement is largely accounted for by increased vitreous chamber depth, as little abnormal change is found in anterior chamber depth or lens thickness in high myopia. 1High myopia is usually defined as myopia in excess of 6 D, equating to an eye length of between 25 and 26 mm. The prevalence of high myopia in the general population is approximately 3% 2 ; however, the prevalence is as high as 16% in certain Southeast Asian populations. 3 One of the most important manifestations of high degrees of myopia is the increased prevalence of retinal degenerative disease, which is largely attributable to the increased stresses placed on the retina of the enlarging eye. 4 The cause of these mechanical demands on the retina are probably twofold. First, the retina thins as it is stretched across the enlarging globe and, second, vitreous motion during eye movement places significant shear forces on the retina. 5,6 There is increasing evidence to confirm that, in enlarging eyes, the retinal elements are str...

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Relationship Among CFH and ARMS2 Genotypes, Macular Pigment Optical Density, and Neuroretinal Function in Persons Without Age-Related Macular Degeneration

Feigl¹,

Morris²,

Brown³

et al. 2012

Arch Ophthalmol

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OBJECTIVES To determine whether there is a difference in neuroretinal function and in macular pigment optical density between persons with high- and low-risk gene variants for age-related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare the results on neuroretinal function to patients with manifest early AMD. METHODS Neuroretinal function was assessed with the multifocal electroretinogram for 32 participants (22 healthy persons with no AMD and 10 patients with early AMD). The 22 healthy participants with no AMD had either high- or low-risk genotypes for CFH (rs380390) and/or ARMS2 (rs10490924). Trough-to-peak response densities and peak-implicit times were analyzed in 5 concentric rings. Macular pigment optical density was assessed by use of customized heterochromatic flicker photometry. RESULTS Trough-to-peak response densities for concentric rings 1 to 3 were, on average, significantly greater in participants with high-risk genotypes than in participants with low-risk genotypes and in persons with early AMD after correction for age and smoking (P < .05). The group peak-implicit times for ring 1 were, on average, delayed in the patients with early AMD compared with the participants with high- or low-risk genotypes, although these differences were not significant. There was no significant correlation between genotypes and macular pigment optical density. CONCLUSIONS Increased neuroretinal activity in persons who carry high-risk AMD genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Neuroretinal function in healthy persons genetically susceptible to AMD may be a useful additional early biomarker (in combination with genetics) of AMD before there is a clinical manifestation.

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Disclosing disease mechanisms with a spatio-temporal summation paradigm

Abstract: The nature of the spatial summation is consistent with the interpretation that early AMD produces a decrease in cone input to post-receptoral mechanisms in the absence of neural remodelling.

Cited by 19 publications

References 39 publications

Functional loss in early age-related maculopathy: the ischaemia postreceptoral hypothesis

Functional loss in early age-related maculopathy: the ischaemia postreceptoral hypothesis

Altered Visual Sensitivity in Axial High Myopia: A Local Postreceptoral Phenomenon?

Relationship Among CFH and ARMS2 Genotypes, Macular Pigment Optical Density, and Neuroretinal Function in Persons Without Age-Related Macular Degeneration

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