High-resolution imaging of photoreceptors in healthy human eyes using an adaptive optics retinal camera

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Abstract

<div class="section"> <a class="named-anchor" id="d388345e152">  </a> <h5 class="section-title" id="d388345e153">Purpose</h5> <p id="Par1">To determine the effects of age on perifoveal cone density in healthy subjects using adaptive optics. </p> </div><div class="section"> <a class="named-anchor" id="d388345e157">  </a> <h5 class="section-title" id="d388345e158">Methods</h5> <p id="Par2">Healthy subjects of various ages were imaged using an adaptive optics retinal camera (RTX-1 <sup>®</sup> Imagine Eyes, Orsay, France). All patients underwent a comprehensive ophthalmologic examination and retinal imaging using spectral-domain optical coherence tomography (Spectralis <sup>®</sup>, Heidelberg Engineering, Heidelberg, Germany). Cone density together with cone spacing and cone mosaic packing were measured in the nasal and temporal area 450 µm from the fovea. A multivariate analysis was performed to determine which of the following parameters were related to a decrease in cone density: age, axial length, central macular thickness, and retrofoveal choroidal thickness. </p> </div><div class="section"> <a class="named-anchor" id="d388345e168">  </a> <h5 class="section-title" id="d388345e169">Results</h5> <p id="Par3">One hundred and sixty-seven eyes of 101 subjects aged 6–78 years were studied. Perifoveal cone density significantly decreased with age ( <i>R</i> <sup>2</sup> = 0.17, <i>p</i><0.01). Inversely, cone spacing increased with age ( <i>R</i> <sup>2</sup>=0.18, <i>p</i><0.01). There was no change in the cone packing mosaic ( <i>p</i>>0.05). The mean coefficient of variation between fellow eyes was 3.9%. Age and axial length were related to a cone density decrease, while choroidal and retinal thicknesses did not affect cone metrics in healthy subjects. </p> </div><div class="section"> <a class="named-anchor" id="d388345e195">  </a> <h5 class="section-title" id="d388345e196">Conclusions</h5> <p id="Par4">A moderate perifoveal cone loss occurs with age. The precise consequences of these findings on visual function should be investigated. In addition to a better understanding of normal retinal anatomy, these results could act as a comparative database for further studies on normal and diseased retinas. </p> </div>

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Choroidal thickness in normal eyes measured using Cirrus HD optical coherence tomography.

Varsha Manjunath, Mohammad Taha, James Fujimoto … (2010)

To examine choroidal thickness and area in healthy eyes using spectral-domain optical coherence tomography (SD-OCT). Retrospective, observational case series. Thirty-four eyes (34 subjects), with no retinal or choroidal disease, underwent high-definition raster scanning using SD-OCT with frame enhancement software. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microm intervals up to 2500 microm temporal and nasal to the fovea. The central 1-mm area of the choroid was also measured, along with foveal thickness of the retina. All measurements were performed by 2 independent observers. Statistical analysis was used to correlate inter-observer findings, choroidal thickness and area measurements with age, and choroidal thickness with retinal foveal thickness. The 34 subjects had a mean age of 51.1 years. Reliable measurements of choroidal thickness were obtainable in 74% of eyes examined. Choroidal thickness and area measurements had strong inter-observer correlation (r = 0.92, P < .0001 and r = 0.93, P < .0001 respectively). Area had a moderate negative correlation with age (r = -0.62, P < .0001) that was comparable to the correlation between mean subfoveal choroidal thickness and age (r = -0.61, P < .0001). Retinal and choroidal thickness were found to be poorly correlated (r = -0.23, P = .18). Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and then thinning again temporally. Mean subfoveal choroidal thickness was found to be 272 microm (SD, +/- 81 microm). Choroidal thickness can be measured using SD-OCT high-definition raster scans in the majority of eyes. Choroidal thickness across the macula demonstrates a thin choroid nasally, thickest subfoveally, and again thinner temporally, and a trend toward decreasing choroidal thickness with age. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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High-resolution imaging with adaptive optics in patients with inherited retinal degeneration.

Jacque L. Duncan, Yuhua Zhang, Jarel Gandhi … (2007)

To investigate macular photoreceptor structure in patients with inherited retinal degeneration using high-resolution images and to correlate the findings with clinical phenotypes and genetic mutations. Adaptive optics scanning laser ophthalmoscopy (AOSLO) images of photoreceptors were obtained in 16 eyes: five with retinitis pigmentosa (RP), three with cone-rod dystrophy (CRD), and eight without retinal disease. A quadratic model was used to illustrate cone spacing as a function of retinal eccentricity. Cone spacing at 1 degrees eccentricity was compared with standard measures of central visual function, including best-corrected visual acuity (BCVA), foveal threshold, and multifocal electroretinogram (mfERG) amplitude and timing. Intervisit variations were studied in one patient with RP and one patient with CRD. Screening of candidate disease genes identified mutations in two patients, one with RP (a rhodopsin mutation) and the other with CRD (a novel RPGR-ORF15 mutation). Cone spacing values were significantly different from normal for patients with RP (P = 0.01) and CRD (P < 0.0001) and demonstrated a statistically significant correlation with foveal threshold (P = 0.0003), BCVA (P = 0.01), and mfERG amplitude (P = 0.008). Although many RP patients showed normal cone spacing within 1 degrees of fixation, cones could not be unambiguously identified in several retinal regions. Cone spacing increased in all CRD patients, even those with early disease. Little variation was observed in cone spacing measured during two sessions fewer than 8 days apart. AOSLO images can be used to study macular cones with high resolution in patients with retinal degeneration. The authors present the first report of cone structure in vivo in patients with mutations in rhodopsin and RPGR-ORF15 and show that macular cones display distinct characteristics, depending on the underlying disease. AOSLO imaging, therefore, can provide new insight into possible mechanisms of cone vision loss in patients with retinal degeneration.

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Intersubject variability of foveal cone photoreceptor density in relation to eye length.

Austin Roorda, Yu Li, Pavan Tiruveedhula (2010)

Adaptive optics scanning laser ophthalmoscopy (AOSLO) under optimized wavefront correction allows for routine imaging of foveal cone photoreceptors. The intersubject variability of foveal cone density was measured and its relation to eye length evaluated. AOSLO was used to image 18 healthy eyes with axial lengths from 22.86 to 28.31 mm. Ocular biometry and an eye model were used to estimate the retinal magnification factor. Individual cones in the AOSLO images were labeled, and the locations were used to generate topographic maps representing the spatial distribution of density. Representative retinal (cones/mm(2)) and angular (cones/deg(2)) cone densities at specific eccentricities were calculated from these maps. The entire foveal cone mosaic was resolved in four eyes, whereas the cones within 0.03 mm eccentricity remained unresolved in most eyes. The preferred retinal locus deviated significantly (P < 0.001) from the point of peak cone density for all except one individual. A significant decrease in retinal density (P < 0.05) with increasing axial length was observed at 0.30 mm eccentricity but not closer. Longer, more myopic eyes generally had higher angular density near the foveal center than the shorter eyes, but by 1°, this difference was nullified by retinal expansion, and so angular densities across all eyes were similar. The AOSLO can resolve the smallest foveal cones in certain eyes. Although myopia causes retinal stretching in the fovea, its effect within the foveola is confounded by factors other than cone density that have high levels of intersubject variability.