Visual Psychophysics / Physiological Optics - ARVO

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ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group – Visual Psychophysics / Physiological Opticsexponential model sufficiently well that 97% had R2 > 0.9; but theparameters differed, and 92% of the data were slightly too steep.These cone densities averaged 43,200, 27,500, 15,000, and 12,200microns per mm2, for the 270, 630, 1440, and 2070 micron locations,with a coefficient of variation of .14, .13, .10, and .10. Cone densityat 630 microns was negatively correlated with the ratio of cones at2070: cones at 630, p < .0001 and p = .0008 for the younger andolder groups, respectively, and uncorrelated to the (unnormalized)density at 2070 microns, p = 0.71 and 0.37. The ratio of cones at2070: cones at 630 averaged 0.45 vs. 0.39, for younger vs. older eyes.Conclusions: Cone density is not characterized by a scalar factor foreither eccentricity or age, nor a model with fixed exponents. Instead,cones from outside the fovea migrate centrally to provide fovealspecialization, and aging further alters the distribution.Commercial Relationships: Ann E. Elsner, Aeon Imaging, LLC(I), Aeon Imaging, LLC (F), Aeon Imaging, LLC (P); Toco Y. Chui,None; Lei Feng, None; Colleen M. McIntyre, None; HongxinSong, Canon (F); Thomas Gast, None; Stephen A. Burns, NoneSupport: NIH Grant EY007624, EY004395, P30EY019008Program Number: 1741Presentation Time: 11:15 AM - 11:30 AMLongitudinal Cone Density Measurements using a CommerciallyAvailable Flood-Illuminated Adaptive Optics Camera inJapanese Macaque Monkeys with Dominantly Inherited DrusenMark E. Pennesi 1 , Keith V. Michaels 1 , Shu Feng 1 , Travis B. Smith 1 ,Anupam K. Garg 1 , Trevor J. McGill 2 , Laurie Renner 2 , MarvinSperling 3 , Kay D. Rittenhouse 3 , Martha Neuringer 2 . 1 Ophthalmology,Casey Eye Institute - OHSU, Portland, OR; 2 Division ofNeuroscience, Oregon National Primate Center, Beaverton, OR;3 External R&D Innovations, Pfizer Inc., San Diego, CA.Purpose: To study the longitudinal changes in cone density in a lineof adult Japanese Macaque monkeys with dominantly inheriteddrusen using a commercially available flood illuminated adaptiveoptics camera.Methods: Twenty male and female Japanese Macaques were sedatedand imaged on the RTx1 Adaptive Optics Camera (Imagine Eyes,Orsay, France) at baseline and six months later. In each animal, aseries of overlapping AO images were obtained starting at the opticnerve and extending temporally through the fovea. Individual imageswere montaged using I2k Align (DualAlignTM). Cone profiles werecounted using a Matlab algorithm (generously provided by Dr.Joseph Carroll) and axial lengths were measured to correct formagnification. Macular drusen were identified with advanced Wekasegmentation (University of Waikato).Results: Cone density plots revealed an anatomic distribution of conephotoreceptors in the macula, but cones within 1.6° of the fovealcenter could not be individually identified. The mean cone densityacross 1.6-3.1° eccentricity was 28843 ± 5284 cones/mm2 after sixmonths. When broken into parafoveal quadrants, cone density washighest in the nasal quadrant and lowest in the superior quadrant forboth time points. The mean baseline age for the animals was 10.8 ±5.5 years. Age was not significantly associated with cone density (p =0.46), nor was it associated with the change in cone density betweenthe time points (p = 0.75). The fraction of area occupied by drusenwas 8.8 ± 12.8 percent. Drusen area also was not significantlyassociated with cone density (p = 0.55), nor was it associated with thechange in cone density between the time points (p = 0.70).Conclusions: Commercially available flood illuminated adaptiveoptics allows for longitudinal measurement of cone density inmacaques with drusen. Preliminary results indicate that age anddrusen load are not associated with a significant change in conedensity over the period studied. Further collections are planned everysix months to assess long-term changes in cone density.Commercial Relationships: Mark E. Pennesi, Pfizer (F); Keith V.Michaels, Pfizer, Inc. (F); Shu Feng, None; Travis B. Smith, Pfizer,Inc. (F); Anupam K. Garg, None; Trevor J. McGill, StemCells,Inc. (C), Pfizer (F), AGTC (F); Laurie Renner, Pfizer (F), AppliedGenetic Technologies Corporation (F); Marvin Sperling, Pfizer Inc.(E); Kay D. Rittenhouse, Pfizer Inc. (E); Martha Neuringer, Pfizer(F), Applied Genetic Technologies Corporation (F)Support: Pfizer Ophthalmology External Research Unit, FFB CD-CL-0808-0469-OHSU, RPB CDA (MEP), RPB Unrestricted - CEI,NIH grant P51OD011092Program Number: 1742Presentation Time: 11:30 AM - 11:45 AMAssessing the Mosaic of Cone Photoreceptors OverlyingSubretinal Drusenoid Deposits in vivo Using Adaptive OpticsSarah Mrejen 1, 2 , Taku Sato 1, 2 , Richard F. Spaide 1, 2 . 1 vitreous retinamacula consultants of New York, New York, NY; 2 LuEsther T MertzRetinal Research Center, Manhattan Eye, Ear and Throat Hospital,New York, NY.Purpose: To investigate the cone photoreceptor mosaic in eyes withpseudodrusen as evidenced by the presence of subretinal drusenoiddeposits (SDD) using adaptive optics (AO) imaging integrated into amultimodal approach.Methods: Consecutive patients with pseudodrusen were examinedusing near-infra-red reflectance (IR) confocal scanning laserophthalmoscopy (SLO) and eye-tracked spectral-domain opticalcoherence tomography (SD-OCT) and a flood-illuminated retinal AOcamera prototype (rtx-1, Imagine Eyes, Orsay, France). The AOimages were acquired between 1 and 5 degrees of retinal eccentricityfrom the foveal center in the areas of SDD. Correlations were madebetween the IR SLO, SD-OCT and the AO images. Cone packingdensity analysis was performed on AO images within 50 x 50 µmwindows in 5 regions of interest overlying and in 5 located betweenSDD. Five patients with soft drusen were evaluated as a comparisongroup.Results: The mean age of 5 patients, all female, with SDD was 71.8years. The SDD identified by combined IR and eye-tracked SD-OCTcorresponded to well-defined areas darker than the surroundinguninvolved areas in the AO images. The mean (±SD) cone packingdensity was 1254 (± 673) cones/mm2 on SDD and 10818 (±1860)cones/mm2 between SDD. Cone density on SDD was approximately11% of cone density between SDD, whereas cone density on softdrusen varied from 60 to 90% of cone density between soft drusen.The cone density between SDD was not significantly different fromthe cone density between soft drusen at the same degree of retinaleccentricity. The lack of visualization of cones on SDD wascorrelated with the disruption of the ellipsoid zone on correspondingSD-OCT. The cone mosaic was well preserved on soft drusen whenthe ellipsoid zone was preserved on corresponding SD-OCT.Conclusions: The lack of visualization of cones on SDD in the AOimages can be due to several possible causes: a change in theirorientation, absence or shortening of their outer segments, or absenceof the cones. Whether the lack of detection of cones on SDD is due toabsent or shortened outer segment or absence of cones, all of theseexplanations imply decreased cone function is possible. Thesefindings suggest these patients with pseudodrusen may experiencedecreased retinal function independent of choroidalneovascularization or retinal pigment epithelium atrophy.Commercial Relationships: Sarah Mrejen, None; Taku Sato,Alcon Japan Ltd. (F); Richard F. Spaide, Topcon (P),Thrombogenics (C), Bausch and Lomb (C)©2013, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permissionto reproduce any abstract, contact the ARVO Office at arvo@arvo.org.
ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group – Visual Psychophysics / Physiological OpticsProgram Number: 1743Presentation Time: 11:45 AM - 12:00 PMAdaptive Optics Scanning Laser Ophthalmoscopy in StargardtDisease Reveals Decreased Cone and Rod DensitiesHongxin Song 1 , Angela Pugliese 2 , Ethan A. Rossi 1 , Lisa R. Latchney 2 ,Edwin M. Stone 3 , Alfredo Dubra 4 , Jennifer J. Hunter 1, 2 , Mina M.Chung 1, 2 . 1 Center for Visual Science, University of Rochester,Rochester, NY; 2 Flaum Eye Institute, University of Rochester,Rochester, NY; 3 Ophthalmology and Visual Science, University ofIowa, Iowa City, IA; 4 Ophthalmology, University of Wisconsin,Milwaukee, WI.Purpose: Stargardt disease (SD) is defined clinically by itsophthalmoscopic features including atrophy and lipofuscin depositionin the retinal pigment epithelium (RPE). The causative ABCA4 geneencodes a protein uniquely expressed in the cone and rod outersegments. The pathologic steps by which mutations in ABCA4 leadto the clinically detectable RPE changes remain unclear. Weinvestigated whether photoreceptor changes precede RPE loss in SDusing adaptive optics scanning laser ophthalmoscopy (AOSLO).Methods: Two brothers with SD, aged 8 and 17 years, underwent acomprehensive eye examination and conventional imaging includingfundus photography and optical coherence tomography (OCT).Genetic testing was performed using a combination of allele-specifictesting and sequencing of the ABCA4 gene. AOSLO images wereobtained at the central fovea and along the inferior and temporalmeridians to generate 10x1.5 degree montages. The center of thefoveal avascular zone was used as the foveal center. Cones werecounted using custom semi-automated cone marking software.Peripheral cones and rods were counted at 100 µm intervals in100x100 µm and 50x50 µm windows respectively. At the fovealcenter, cones were counted in a 50x50 µm window.Results: Genetic testing showed the presence of three likely diseasecausingmutations: Gly863Ala, Gly1961Glu, and Arg2030Stop. Theolder brother had visual acuity 20/150 with a central scotoma andmacular RPE atrophy with no peripheral flecks. His brother hadvisual acuity 20/30 with subtle RPE stippling in the macula. In bothbrothers, OCT confirmed central retinal thinning. AOSLO revealedthat rod density was decreased to ~30% of normal in the peripheralmacula; these areas appeared normal by ophthalmoscopy and OCT.Cones in the peripheral macula showed a dark, low reflectiveappearance with density 30% of normal. No cones were detectable inthe foveal center of the older brother. In the younger brother, fovealcones were enlarged with low density.Conclusions: This study provides the first in vivo images of bothrods and cones in SD. Although the primary clinical features of SDare changes in the RPE, AOSLO reveals decreased density of bothcones and rods in areas that appear normal by conventional imagingmethods. These findings suggest that loss of cone and rodphotoreceptors precedes clinically detectable RPE disease in SD.Commercial Relationships: Hongxin Song, Canon (F); AngelaPugliese, None; Ethan A. Rossi, Canon Inc. (F); Lisa R. Latchney,None; Edwin M. Stone, None; Alfredo Dubra, US Patent No:8,226,236 (P); Jennifer J. Hunter, Polgenix, Inc. (F); Mina M.Chung, Canon (F)Support: NEI EY021786, EY014375, EY001319, Edward N. &Della L. Thome Memorial Foundation to Mina Chung, Research toPrevent Blindness Unrestricted/Challenge Grant, BurroughsWellcome Fund to Alfredo Dubra-SuarezProgram Number: 1744Presentation Time: 12:00 PM - 12:15 PMCone structure imaged with Adaptive Optics Scanning LaserOphthalmoscopy in eyes with Non-Neovascular Age-relatedMacular DegenerationShiri Zayit-Soudry 1 , Reema Syed 1 , Kavitha Ratnam 1 , MorenoMenghini 1 , Austin Roorda 2 , Jacque L. Duncan 1 .1 Ophthalmology/Retina Division, University of California, SanFrancisco, San Francisco, CA; 2 School of Optometry, University ofCalifornia, Berkeley, Berkeley, CA.Purpose: To evaluate cone structure using Adaptive Optics ScanningLaser Ophthalmoscopy (AOSLO) in eyes with non-neovascular agerelated macular degeneration (AMD), and to correlate progression ofAOSLO-derived cone measures with standard measures of macularstructure. High resolution imaging of cone photoreceptor morphologyand quantitative measures of cone structure may enhanceunderstanding of the pathophysiology of vision loss in AMD andprovide a sensitive biomarker for disease progression.Methods: AOSLO macular images were obtained over 12 to 21months from 7 patients with non-neovascular AMD including 4 eyeswith geographic atrophy (GA) and 6 eyes with drusen. AOSLOimages were precisely superimposed onto color, infrared andautofluorescence fundus photographs and spectral domain opticalcoherence tomography (SD-OCT) images to allow direct correlationof cone parameters with macular structure. Cone spacing wasmeasured for each visit in selected regions including areas overdrusen (n=29), at the margin of GA (n=14), and regions withoutevidence of drusen or GA on fundus photos or SD-OCT (n=13) andcompared to normal, age-related values.Results: AOSLO imaging revealed intact cones up to the GA edgeand overlying drusen, although subtle mosaic irregularity andreduced reflectivity often resulted in a dark signal surrounding GAmargins and drusen. At baseline, cone spacing measures were normalat all study locations but 2 GA margin locations and 4 drusenlocations. Although progression of GA was observed in most studyeyes with standard clinical measures, AOSLO longitudinal trackingshowed mild increases in cone spacing in 3 drusen locations, butstable cone spacing measures in all other drusen and GA marginlocations.Conclusions: AOSLO provides adequate resolution for quantitativemeasurement of cone structure at the margin of GA and over drusenin eyes with non-neovascular AMD, providing insight into thepathophysiology of GA progression. Despite reflectivity changesnoted over drusen and at GA margins, cone spacing was oftenpreserved at these locations and remained stable over time,suggesting changes in cone spacing may not represent a primarystructural change in AMD progression.Commercial Relationships: Shiri Zayit-Soudry, None; ReemaSyed, None; Kavitha Ratnam, None; Moreno Menghini, None;Austin Roorda, US Patent #6890076 (P), US Patent #7118216 (P),UC Berkeley (P); Jacque L. Duncan, NoneSupport: NIH EY014375, Novartis Institutes for BiomedicalResearch, NEI Core grant EY002162, American Health AssistanceFoundation (AHAF) Macular Degeneration Research Grant (MDR),Foundation Fighting Blindness, Research To Prevent Blindness, ThatMan May SeeProgram Number: 1745Presentation Time: 12:15 PM - 12:30 PMAdaptive Optics Imaging of Photoreceptors following Repair ofRhegmatogenous Retinal DetachmentsMeenakashi Gupta 1 , Michael Dubow 1, 2 , Alexander Pinhas 1, 2 , NishitShah 1 , Patricia Garcia 1 , Gennady Landa 1 , Yusufu N. Sulai 3 , AlfredoDubra 4 , Richard B. Rosen 1 . 1 New York Eye and Ear Infirmary, NewYork, NY; 2 Mount Sinai School of Medicine, Mount Sinai Hospital,©2013, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permissionto reproduce any abstract, contact the ARVO Office at arvo@arvo.org.
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