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Adam M Dubis, Robert F Cooper, Joseph Carroll, Alfredo Dubra, Michel Michaelides; Quantifying Photoreceptor Reflectance: When density is not enough. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5201.
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© ARVO (1962-2015); The Authors (2016-present)
Current analysis of photoreceptor mosaics from adaptive optics images involves quantifying photoreceptor mosaic integrity either with metrics such as cone spacing and density or qualitative terms such as hyper- or hypo- reflective cells. Development of a metric to describe reflectance is important to monitor the integrity of individual cells in response to treatment
Eight subjects with a range of retinal pathologies were imaged using a custom-build adaptive optics ophthalmoscope. Images were registered and then averaged. To quantify reflectance, the local maximum was identified for 200 cones and 600 rods per subject. Locations were selected between 5-8 deg temporally with sufficient cones and rods, and free of vessel shadows. The profile was fit to a 2D Difference of Gaussian, to objectively define its border. Reflectance was taken as the average of reflectance values from the full width at half maximum of the profile. The reflectivity values for rod and cone photoreceptors were normalized to the average intensity of the image.
Single cases of Poppers Maculopathy, Bradyopsia and an RPGR carrier had normal cone and rod densities, and had > 89% of their photoreceptors with a normalized average reflectance (NAR)>1. The AMN patient had a reduction in cone density, with 60% of cones having a NAR>1; while 92% of rods were>1. Two other RPGR carriers had regions of both normal and decreased photoreceptor density. Interestingly, only 48% of the NAR>1, while 100% of the rods were>1. This is likely due to the observed rod hyper-reflectivity. Two patients with achromatopsia had 0% NAR>1, while 96% of rods were>1.
Quantification of relative reflectance holds promise as a biomarker of photoreceptor health/disease across different diseases. This is particularly valuable given that gene augmentation therapies will not result in new cells and therefore geometrical descriptors of the photoreceptor mosaic will not be adequate to monitor therapeutic success/progression. Long- term usefulness of this metric will be based on longitudinal repeatability in normal and diseased retina.
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