We describe a new technique, high fidelity Imaging Retinal Densitometry (IRD), which probes the functional integrity of the outer retinal complex. We demonstrate the ability of the technique to map visual pigment optical density and synthesis rates in eyes with and without macular disease. A multispectral retinal imaging device obtained precise measurements of retinal reflectance over space and time. Data obtained from healthy controls and 5 patients with intermediate AMD, before and after photopigment bleaching, were used to quantify visual pigment metrics. Heat maps were plotted to summarise the topography of rod and cone pigment kinetics and descriptive statistics conducted to highlight differences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v = 0.043 SD 0.019 min −1 and v = 0.119 SD 0.046 min −1 , respectively) were approximately half those observed in healthy controls (v = 0.079 SD 0.024 min −1 for rods and v = 0.206 SD 0.069 min −1 for cones). By mapping visual pigment kinetics across the central retina, high fidelity IRD provides a unique insight into outer retinal complex function. This new technique will improve the phenotypic characterisation, diagnosis and treatment monitoring of various ocular pathologies, including AMD. Continuous photoreceptor function is dependent on the constant renewal of visual pigment molecules by a physiological process known as the visual cycle 1. Remarkably, the key enzymatic steps in the canonical visual cycle reside not in the photoreceptors but in the cells that nourish them, the retinal pigment epithelium (RPE). More specifically, the RPE converts the retinoid all-trans retinol back to 11-cis retinal via a series of relatively slow enzymatic reactions which, in the healthy eye, determine the rate at which visual pigment molecules can regenerate 2. Hence by measuring rod photoreceptor visual pigment synthesis rates we can probe a key aspect of RPE physiology. The RPE also supports the regeneration of visual pigments in cone photoreceptors but an additional visual cycle pathway that involves the neural retina's Müller Cells is also involved 2,3. The RPE, Bruch's membrane and the choriocapillaris, are associated with many ocular pathologies, most notably age-related macular degeneration (AMD) the developed world's leading cause of sight loss 4,5. In AMD, an increase in the thickness of basal laminar deposits, the presence of soft drusen and choriocapillaris drop out all work to impair normal RPE function 5. Hence, by measuring visual pigment synthesis rates we not only obtain information about the status of a vital physiological process, the visual cycle, but also information about the functional integrity of the outer retinal complex i.e. the photoreceptors, RPE, Müller Cells, Bruch's membrane and the choriocapillaris. Fortunately, visual pigment synthesis rates can be measured by recording the subtle changes in retinal reflectance associated with the visual cycle using a technique called densitometry 6,7. Although the...
No effect on retinal vascular permeability or retinal electrophysiology was apparent after intravitreal administration of H-7 or Lat-B at doses that increase outflow facility and lower IOP when given intracamerally.
HiPERCAM is a five channel fast photometer to study high temporal variability of the universe, covering from 0.3 to 1.0 microns in five wavebands. HiPERCAM uses custom-made 2Kx1K split-frame transfer CCDs mounted in separate compact camera heads and cooled by thermoelectric coolers to 180K. The demands on the readout system are very unique to this instrument in that all five CCDs are operated in a pseudo drift window mode along with the normal windowing, binning and full-frame modes. The pseudo drift mode involves reading out small window regions from 2 quadrants of each CCD, with the possibility to exceed 1 kHz window rates per output channel. The CCDs are custom manufactured by Teledyne e2v to allow independent serial clock controls for each output. The devices are manufactured in standard and deep-depletion processes with appropriate anti-reflection coatings to achieve high quantum efficiencies in each of the five wavebands. An ESO NGC controller has been configured to control and readout all five CCDs. The data acquisition software has been modified to provide GPS timestamping of the data and access to the acquired data in real time for the data reduction software. The instrument has had its first light and first science observations on the 4.2m William Herschel Telescope, La Palma during a commissioning run in October 2017 and subsequently on the 10.4m Gran Telescopio Canarias in February 2018 and science observations in April 2018. This paper will present the details of the preamplifier electronics, configuration of the readout electronics and the data acquisition software to support the unique readout modes along with the overall performance of the instrument.
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