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1. Characterizing Macular Neovascularization in Myopic Macular Degeneration and Age-Related Macular Degeneration Using Swept Source OCTA

Author

Sayah DN, Garg I, Katz R, Zhu Y, Cui Y, Zeng R, Tandias R, Moon JY, Vingopoulos F, Wescott HE, Baldwin G, Wang K, Elze T, Ludwig CA, Vavvas DG, Miller JW, Husain D, Kim LA, Patel NA, and Miller JB

Subjects
macular neovascularization, age-related macular degeneration, high myopia, swept source, oct angiography, Ophthalmology, RE1-994
Abstract

Diane N Sayah,1– 3 Itika Garg,1,2 Raviv Katz,1,2 Ying Zhu,1,4 Ying Cui,1,5 Rebecca Zeng,1,2 Rachel Tandias,1,2 Jade Y Moon,1,2 Filippos Vingopoulos,1,2 Hannah E Wescott,1,2 Grace Baldwin,1,2 Kira Wang,1,2 Tobias Elze,1,2 Cassie Ann Ludwig,1,2 Demetrios G Vavvas,1,2 Joan W Miller,1,2 Deeba Husain,1,2 Leo A Kim,1,2 Nimesh A Patel,1,2 John B Miller1,2 1Harvard Retinal Imaging Lab, Boston, MA, USA; 2Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; 3College of Optometry, University of Houston, Houston, TX, USA; 4Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of ChinaCorrespondence: John B Miller, Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 243 Charles St, Boston, MA, 02114, USA, Tel +1 617 573-3750, Fax + 1 617 573-3698, Email John_Miller@meei.harvard.eduPurpose: Visual prognosis and treatment burden for macular neovascularization (MNV) can differ between myopic macular degeneration (MMD) and age-related macular degeneration (AMD). We describe and compare MNV associated with MMD and AMD using swept-source (SS)-OCTA.Patients and Methods: Adult patients with documented MNV associated with MMD or AMD were consecutively recruited. Qualitative and quantitative features were assessed from 6x6mm angiograms, including the MNV area and vessel density (VD). Descriptive statistics and linear regression analyses were carried out.Results: Out of 75 enrolled eyes with diagnosed MNV (30 MMD-MNV and 45 AMD-MNV; mean age 55± 19 and 75± 8 years, respectively), 44 eyes had discernible MNV (11 MMD-MNV and 33 AMD-MNV) on SS-OCTA at the time of the study and were included in the analysis. The MMD-MNV group exhibited a three-fold smaller sized MNV (p=0.001), lower greatest linear dimension (p=0.009) and greatest vascular caliber (p< 0.001) compared to AMD-MNVs, and had a higher prevalence of tree-in-bud pattern. Eyes with AMD showed a higher prevalence of type 1 MNVs with medusa pattern. There was no difference in the location of the MNV, shape’s regularity, margins, presence of core vessel, capillary fringe, peripheral loops, or perilesional dark halo (p> 0.05) between both conditions. After adjustment, decreased MNV area and increased VD were associated with the tree-in-bud pattern, whereas the diagnosis did not significantly influence those parameters.Conclusion: While larger studies are warranted, this study is the first to describe and compare MMD-MNV and AMD-MNV using SS-OCTA, providing relevant clinical insight on MNV secondary to MMD and AMD. These findings also further validate OCTA as a powerful tool to detect and characterize MNV non-invasively.Keywords: macular neovascularization, age-related macular degeneration, high myopia, swept source, OCT angiography

Published
2023

2. Quantitative Wide-Field Swept-Source Optical Coherence Tomography Angiography and Visual Outcomes in RAO

Author

Lu Y, Cui Y, Zhu Y, Lu ES, Zeng R, Garg I, Katz R, Le R, Wang JC, Vavvas DG, Husain D, Miller JW, Wu D, and Miller JB

Subjects
wf ss-octa, rao, brao, crao, etdrs, ari network, Ophthalmology, RE1-994
Abstract

Yifan Lu,1,2,&ast; Ying Cui,1,3,&ast; Ying Zhu,1,4,&ast; Edward S Lu,1 Rebecca Zeng,1 Itika Garg,1 Raviv Katz,1 Rongrong Le,1,5 Jay C Wang,1 Demetrios G Vavvas,1,2 Deeba Husain,1,2 Joan W Miller,1,2 David Wu,1,2 John B Miller1,2 1Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA; 2Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 3Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Wenzhou Medical University Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: John B Miller, Retina Service, Mass, Eye and Ear Infirmary, Harvard Medical School, 243 Charles St, Boston, MA, 02114, USA, Tel +1 (617) 573-3750, Fax +1 (617) 573-3698, Email john_miller@meei.harvard.eduPurpose: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcomes and is associated with an increased risk of stroke and cardiovascular events. Wide-field swept-source OCT-A (WF SS-OCTA) can provide quick and non-invasive angiographic information with a wide field of view. Here, we looked for associations between OCT-A vascular imaging metrics and vision in RAO patients.Methods: Patients with diagnoses of central (CRAO) or branched retinal artery occlusion (BRAO) were included. 6mm × 6mm Angio and 15mm × 15mm AngioPlex Montage OCT-A images were obtained for both eyes in each patient using Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm × 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Non-perfusion area (NPA) was manually measured using 15mm × 15mm images. A linear regression model was utilized to identify correlation between imaging metrics and vision. P-values less than 0.05 were considered as statistically significant.Results: Twenty-five subjects were included. For RAO eyes, there was a statistically significant inverse correlation between retinal thickness as well as superficial capillary plexus (SCP) vessel density (VD) and vision. An inverse correlation was found between deep capillary plexus (DCP) VD and vision without statistical significance. There was a positive correlation between choroidal thickness as well as choroidal volume and vision without statistical significance. No significant correlation was found between the metrics and vision in contralateral eyes. For NPA and vision, no significant correlation was identified.Conclusion: This is the first study to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between retinal vascular imaging metrics and visual outcomes. The results of this study provide a basis to understand the structural changes involved in vision in RAO and may guide management of RAO and prevention of cerebral stroke and cardiovascular accidents.Keywords: WF SS-OCTA, RAO, BRAO, CRAO, ETDRS, ARI network

Published
2023

3. Quantitative Comparison Of Microvascular Metrics On Three Optical Coherence Tomography Angiography Devices In Chorioretinal Disease

Author

Lu Y, Wang JC, Zeng R, Katz R, Vavvas DG, Miller JW, and Miller JB

Subjects
OCTA, Angiovue, Angioplex, Triton, Zeiss, Optovue, Ophthalmology, RE1-994
Abstract

Yifan Lu,1,2,* Jay C Wang,1–3,* Rebecca Zeng,2 Raviv Katz,2 Demetrios G Vavvas,2,3 Joan W Miller,2,3 John B Miller1–3 1Department of Ophthalmology, Harvard Medical School, Boston, Ma, USA; 2Harvard Retinal Imaging Laboratory, Massachusetts Eye and Ear, Boston, Ma, USA; 3Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA*These authors contributed equally to this workCorrespondence: John B MillerRetina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 243 Charles St, Boston, MA 02114, USATel +1 617 573 3750Fax +1 617 573 3698Email john_miller@meei.harvard.eduPurpose: Optical coherence tomography angiography (OCT-A) has emerged as a novel tool for the non-invasive imaging and evaluation of the retinal microvasculature. There is little existing literature that compares OCT-A microvasculature metrics across different OCT-A devices in chorioretinal diseases. Herein, we examined these metrics on three available OCT-A platforms.Patients and methods: All subjects were scanned on each of three OCT-A devices: Optovue Avanti Angiovue, Topcon DRI-OCT Triton Swept-Source OCT, and Zeiss Cirrus 5000-HD-OCT Angioplex. Two investigators independently measured foveal avascular zone (FAZ) area. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities (VD) were calculated from binarized images with ImageJ software. Image quality across devices was qualitatively compared. Interclass correlation coefficient (ICC), Bland-Altman analysis, repeated measures ANOVA, and post-hoc tests were performed for statistical analysis.Results: Thirteen eyes of seven patients with chorioretinal diagnoses were reviewed. ICC for FAZ measurement was 0.95. There was no significant difference in FAZ area across the three devices (p= 0.792). There was a significant difference in the SCP VD between the OCT-A devices (Triton 0.344 ± 0.013, Angiovue 0.323 ± 0.013, Angioplex 0.367 ± 0.014, p < 0.05). Significantly greater DCP VD was observed with Angioplex (0.385 ± 0.010) in comparison to both Triton (0.331 ± 0.009) and Angiovue (0.341 ± 0.020). A comparison of image quality revealed that Angiovue gives the highest quality, followed by Angioplex and Triton.Conclusion: Core macular microvasculature metrics are now readily accessible on a variety of available OCT-A devices. While the FAZ can be reliably measured across all three devices in this study, there were significant differences for the vessel density in both the SCP and DCP. As a result, clinicians should be careful when comparing microvasculature metrics across different devices when using patient data in multicenter research investigations and clinical trials.Keywords: OCTA, Angiovue, Angioplex, Triton, Zeiss, Optovue

Published
2019

4. Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis

Author

Reddy CG, Miller JW, Abode-Iyamah KO, Safayi S, Wilson S, Dalm BD, Fredericks DC, Gillies GT, Howard III MA, and Brennan TJ

Subjects
Neuropathic pain, Sheep models, Gait analysis, Spinal cord stimulation, Unit recordings, Medicine (General), R5-920
Abstract

Chandan G Reddy,1 John W Miller,1 Kingsley O Abode-Iyamah,1 Sina Safayi,2 Saul Wilson,1 Brian D Dalm,1 Douglas C Fredericks,3 George T Gillies,4 Matthew A Howard III,1 Timothy J Brennan5 1Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA; 2Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA, USA; 3Department of Orthopedics and Rehabilitation, University of Iowa Carver College of Medicine, Iowa City, IA, USA; 4Department of Mechanical and Aerospace Engineering, University of Virginia, Charlottesville, VA, USA; 5Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City, IA, USA Background: It is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise. Purpose: Additionally, the small anatomic scale of current SCS animal models is a barrier to more translational research. Methods: Using chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact. Results: Detectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI. Conclusion: To our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS. Keywords: neuropathic pain, sheep models, gait analysis, spinal cord stimulation, unit recordings

Published
2018

5. Novel grid combined with peripheral distortion correction for ultra-widefield image grading of age-related macular degeneration

Author

Oellers P, Laíns I, Mach S, Garas S, Kim IK, Vavvas DG, Miller JW, Husain D, and Miller JB

Subjects
Ultra-widefield, autofluorescence, macular degeneration, grid, periphery, drusen, retinal pigment epithelium changes, Ophthalmology, RE1-994
Abstract

Patrick Oellers,1,* Inês Laíns,1,2,* Steven Mach,1 Shady Garas,1 Ivana K Kim,1 Demetrios G Vavvas,1 Joan W Miller,1 Deeba Husain,1 John B Miller1 1Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; 2Faculty of Medicine, University of Coimbra, Coimbra, Portugal *These authors contributed equally to this work Purpose: Eyes with age-related macular degeneration (AMD) often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF) imaging.Methods: This is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images.Results: Peripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD.Conclusion: We present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation for the exploration of peripheral retinal pathology associated with AMD. Keywords: ultra-widefield, autofluorescence, macular degeneration, grid, periphery, drusen, retinal pigment epithelium changes

Published
2017

6. Effect of hydrogen addition on criteria and greenhouse gas emissions for a marine diesel engine

Author

Pan, H, Pournazeri, S, Princevac, M, Miller, JW, Mahalingam, S, Khan, MY, Jayaram, V, and Welch, WA

Subjects
Dual fuel internal combustion engine, Hydrogen addition, Diesel engine, PM, NOx, Fuel consumption, Energy, Engineering, Chemical Sciences
Abstract

Hydrogen remains an attractive alternative fuel to petroleum and a number of investigators claim that adding hydrogen to the air intake manifold of a diesel engine will reduce criteria emissions and diesel fuel consumption. Such claims are appealing when trying to simultaneously reduce petroleum consumption, greenhouse gases and criteria pollutants. The goal of this research was to measure the change in criteria emissions (CO, NOx, and PM 2.5) and greenhouse gases such as carbon dioxide (CO2), using standard test methods for a wide range of hydrogen addition rates. A two-stroke Detroit Diesel Corporation 12V-71TI marine diesel engine was mounted on an engine dynamometer and tested at three out of the four loads specified in the ISO 8178-4 E3 emission test cycle and at idle. The engine operated on CARB ultra-low sulfur #2 diesel with hydrogen added at flow rates of 0, 22 and 220 SLPM. As compared with the base case without hydrogen, measurements showed that hydrogen injection at 22 and 220 SLPM had negligible influence on the overall carbon dioxide specific emission, EFCO2. However, in examining data at each load the data revealed that at idle EFCO2 was reduced by 21% at 22 SLPM (6.9% of the added fuel energy was from hydrogen) and 37.3% at 220 SLPM (103.1% of the added fuel energy was from hydrogen). At all other loads, the influence of added hydrogen was insignificant. Specific emissions for nitrogen oxides, EFNOx, and fine particulate matters, EFPM 2.5, showed a trade-off relationship at idle. At idle, EFNO x was reduced by 28% and 41% with increasing hydrogen flow rates, whilst EFPM2.5 increased by 41% and 86% respectively. For other engine loads, EFNOx and EFPM2.5 did not change significantly with varying hydrogen flow rates. One of the main reasons for the greater impact of hydrogen at idle is that the contribution of hydrogen to the total fuel energy is much higher at idle as compared to the other loads. The final examination in this paper was the system energy balance when hydrogen is produced by an on-board electrolysis unit. An analysis at 75% engine load showed that hydrogen production increased the overall equivalent fuel consumption by 2.6% at 22 SLPM and 17.7% at 220 SLPM. © 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

Published
2014

7. Transcobalamin C776G genotype modifies the association between vitamin B12 and homocysteine in older Hispanics

Author

Garrod, MG, Allen, LH, Haan, MN, Green, R, and Miller, JW

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Aging, Rare Diseases, Genetics, Nutrition, Aged, Analysis of Variance, California, Female, Genotype, Health Surveys, Hispanic or Latino, Homocysteine, Homozygote, Humans, Hyperhomocysteinemia, Logistic Models, Male, Methylmalonic Acid, Middle Aged, Polymorphism, Single Nucleotide, Transcobalamins, Vitamin B 12, Vitamin B Complex, White People, transcobalamin, polymorphism, homocysteine, vitamin B12, Hispanic elderly, Food Sciences, Human Movement and Sports Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

Background/objectivesA common polymorphism, C776G, in the plasma B12 transport protein transcobalamin (TC), encodes for either proline or arginine at codon 259. This polymorphism may affect the affinity of TC for B12 and subsequent delivery of B12 to tissues.Subjects/methodsTC genotype and its associations with indicators of B12 status, including total B12, holotranscobalamin (holoTC), methylmalonic acid and homocysteine, were evaluated in a cohort of elderly Latinos (N=554, age 60-93 years) from the Sacramento Area Latino Study on Aging (SALSA).ResultsThe distribution of TC genotypes was 41.3% homozygous reference (776CC) and 11.6% homozygous variant (776GG). No differences between the homozygous genotypes were observed in total B12, holoTC, methylmalonic acid or homocysteine. The holoTC/total B12 ratio was lower in the 776GG group compared with the 776CC group (P=0.04). Significant interactions of TC genotype with total B12 (P=0.04) and with holoTC (P< or =0.03) were observed such that mean homocysteine concentrations and the odds ratios for hyperhomocysteinemia (>13 micromol/l) were higher in the 776CC subjects compared with all carriers of the G allele (776CG and 776GG combined) when total B12 (

Published
2010

10. Fluvial Features on Titan and Earth: Lessons from Planform Images in Low-resolution SAR

Author

Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences, Miller, JW, Birch, SPD, Hayes, AG, Malaska, MJ, Lopes, RMC, Schoenfeld, AM, Corlies, PM, Burr, DM, Farr, TG, Perron, JT, Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences, Miller, JW, Birch, SPD, Hayes, AG, Malaska, MJ, Lopes, RMC, Schoenfeld, AM, Corlies, PM, Burr, DM, Farr, TG, and Perron, JT

Abstract

Abstract Cassini Synthetic Aperture Radar (SAR) images of Titan’s surface revealed river networks strikingly similar to those on Earth. However, Cassini SAR has low spatial resolution and image quality compared to data used to map channels on Earth, so traditional methods for characterizing river networks might not yield accurate results on Titan. We mapped terrestrial analog networks with varying resolutions and image qualities to determine which geomorphologic metrics were invariant with scale or resolution. We found that branching angle and drainage density varied significantly with image resolution, and we therefore expect the actual drainage density of Titan’s channel networks to be significantly higher than the values calculated from Cassini data. Calculated network geometry did not change predictably with resolution and would therefore not be an ideal metric for interpreting Titan’s channel networks. The measured channel width, basin length and width, and drainage area all behaved predictably as resolution varied, leading us to conclude that these metrics could be applied to Cassini data. We then mapped all observable fluvial features on Titan—excluding those in the highly incised labyrinth terrains—visible in the Cassini data set. In our new maps, we observe differences in basin shapes between Titan’s polar and equatorial regions and dichotomies in the relative channel density between the northern and southern midlatitudes and poles of Titan: channels are concentrated at the poles and southern midlatitudes. These patterns may reflect differences in bedrock material and/or different climate histories.

Published
2023

11. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A beta, tau, immunity and lipid processing (vol 51, pg 414, 2019)

Author

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Damotte, V, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Moreno-Grau, S, Olaso, R, Raybould, R, Chen, YN, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, LM, Bacq, D, Denning, N, Jian, XQ, Zhao, Y, Del Zompo, M, Fox, NC, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Sanchez-Garcia, F, Patel, Y, Brody, JA, Dombroski, BA, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewicz, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, WS, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Sordon, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Munoz-Fernadez, C, Sussams, R, Lin, HH, Fairchild, TJ, Benito, YA, Holmes, C, Karamujic-Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roshchupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernandez, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Diez-Fairen, M, Rivadeneira, F, Petersen, RC, Deramecourt, V, Alvarez, I, Salani, F, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AGA, Royall, DR, Dufouil, C, Maletta, RG, de Rojas, I, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Quintela, I, Carracedo, A, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frolich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JA, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JSK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, CH, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Kolsch, H, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hull, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, GE, Jin, LW, Leonenko, G, Real, LM, Jun, GR, Baldwin, CT, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jockel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nothen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, Mckee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O'Bryant, S, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, WR, Mead, S, Peskind, E, Cribbs, DH, Rossor, M, Pierce, A, Ryan, NS, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Caltagirone, C, Bossu, P, Orfei, MD, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Slifer, S, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tang, M, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Saba, Y, Pilotto, A, Bullido, MJ, Peters, O, Crane, PK, Bennett, D, Bosco, P, Coto, E, Boccardi, V, De Jager, PL, Lleo, A, Warner, N, Lopez, OL, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Nicolas, G, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Clarimon, J, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O'Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ramirez, A, Wang, LS, Ruiz, A, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, ADGC, EADI, Cohorts Heart Aging Res Genomic, and Genetic Environm Risk AD Defining

Published
2019

12. Progression characteristics of ellipsoid zone loss in macular telangiectasia type 2

Author

Pauleikhoff, D, Bonelli, R, Dubis, AM, Gunnemann, F, Rothaus, K, Charbel Issa, P, Heeren, TFC, Peto, T, Clemons, TE, Chew, EY, Bird, AC, Sallo, FB, Bakri, S, Bernstein, PS, Blodi, B, Brucker, A, Bucher, F, Issa, PC, Chung, M, Comer, G, Constable, I, Cooney, M, Do, D, Duncan, J, Egan, C, Elman, MJ, Fawzi, A, Friedlander, M, Gaudric, A, Gillies, MC, Goldberg, R, Googe, JM, Guymer, R, Higgins, P, Holz, F, Houghton, O, Hoyng, CB, Hubschman, J-P, Jhaveri, C, Khanani, A, Lally, D, Lee, C, Lee, M, Miller, JW, Miller, D, Moisseiev, J, Murphy, R, Narayanan, R, Randhawa, S, Raphaelian, PV, Rich, R, Rosen, R, Rosenfeld, P, Ruys, J, Sahel, J-A, Schwartz, S, Singerman, L, Sneed, S, Soubrane, G, Vingerling, JR, Warrow, D, Weinberg, D, Wolf, S, Wykoff, C, Yan, J, Yannuzzi, LA, Zhuk, SA, Pauleikhoff, D, Bonelli, R, Dubis, AM, Gunnemann, F, Rothaus, K, Charbel Issa, P, Heeren, TFC, Peto, T, Clemons, TE, Chew, EY, Bird, AC, Sallo, FB, Bakri, S, Bernstein, PS, Blodi, B, Brucker, A, Bucher, F, Issa, PC, Chung, M, Comer, G, Constable, I, Cooney, M, Do, D, Duncan, J, Egan, C, Elman, MJ, Fawzi, A, Friedlander, M, Gaudric, A, Gillies, MC, Goldberg, R, Googe, JM, Guymer, R, Higgins, P, Holz, F, Houghton, O, Hoyng, CB, Hubschman, J-P, Jhaveri, C, Khanani, A, Lally, D, Lee, C, Lee, M, Miller, JW, Miller, D, Moisseiev, J, Murphy, R, Narayanan, R, Randhawa, S, Raphaelian, PV, Rich, R, Rosen, R, Rosenfeld, P, Ruys, J, Sahel, J-A, Schwartz, S, Singerman, L, Sneed, S, Soubrane, G, Vingerling, JR, Warrow, D, Weinberg, D, Wolf, S, Wykoff, C, Yan, J, Yannuzzi, LA, and Zhuk, SA

Abstract

PURPOSE: To investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity. METHODS: Participants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral-Domain Optical Coherence Tomograph (SD-OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models. RESULTS: A total of 134 eyes of 70 patients were included (85 eyes with follow-up, mean 4.7 years, range: 1.4-8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non-linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length had a significant linear effect on EZ break area (b = 1.06, p < 0.001) and could predict it. The location of the EZ break had a significant impact on visual acuity. CONCLUSION: Ellipsoid zone (EZ) loss in MacTel has a non-linear progression characteristic, and its rate depends on area size at baseline, which must be taken into account at sample selection in clinical trials. Our results show a good correlation of linear and area measures of EZ loss and a segregation of best-corrected visual acuity by EZ location, which may help routine clinical practice.

Published
2019

13. Meta-analysis of genetic association with diagnosed Alzheimer's disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Author

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Aloso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Zompo, MD, Fox, NC, Grove, ML, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Garcia, FS, Patel, Y, Brody, JA, Dombroski, B, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewics, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, W, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Pichler, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Fernadez, CM, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth Jr, WT, Montine, TJ, Frisardi, V, Ortega-Cubero, S, Rivadeneira, F, Petersen, RC, Deramecourt, V, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Caltagirone, C, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, Moreno-Grau, S, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Baldwin, CT, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JI, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Cribbs, DH, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, G, Jin, LW, Leonenko, G, Jun, G, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Coto, E, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, W, Mead, S, Peskind, E, Rosser, M, Pierce, A, Ryan, N, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Bossù, P, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Crane, PK, Bennett, DA, Boccardi, V, De Jager, PL, Warner, N, Lopez, OL, McDonough, S, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O’Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ruiz, A, Ramirez, A, Wang, LS, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, Bis, JC [0000-0002-3409-1110], Garnier, JG [0000-0003-4991-763X], Smith, AV [0000-0001-9088-234X], Denning, N [0000-0001-8467-7382], Vandenberghe, R [0000-0001-6237-2502], Himali, JJ [0000-0003-1391-9481], Rodriguez-Rodriguez, E [0000-0001-7742-677X], Frisardi, V [0000-0003-0764-7387], Ortega-Cubero, S [0000-0003-0520-9439], Hanon, O [0000-0002-4697-122X], Brice, A [0000-0002-0941-3990], Albin, RL [0000-0002-0629-608X], Buxbaum, JD [0000-0001-8898-8313], Bass, NJ [0000-0002-4481-778X], Fisher, E [0000-0003-2850-9936], Bayer, A [0000-0002-7514-248X], Gallacher, J [0000-0002-2394-5299], Brayne, C [0000-0001-5307-663X], Riedel-Heller, S [0000-0003-4321-6090], Al-Chalabi, A [0000-0002-4924-7712], and Apollo - University of Cambridge Repository

Subjects
Aging, 4202 Epidemiology, Genome-wide association study, Disease, Neurodegenerative, Biology, 3101 Biochemistry and Cell Biology, Alzheimer's Disease, 3105 Genetics, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Acquired Cognitive Impairment, Genetics, medicine, 2.1 Biological and endogenous factors, Dementia, Gene, 030304 developmental biology, Genetic association, 2 Aetiology, 0303 health sciences, Prevention, Human Genome, 42 Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Lipid metabolism, medicine.disease, Brain Disorders, 3. Good health, Meta-analysis, Neurological, Alzheimer's disease, 030217 neurology & neurosurgery, 31 Biological Sciences
Abstract

IntroductionLate-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly1, and risk is partially driven by genetics2. Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS)3–8. To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci (IQCK, ACE, ADAM10, and ADAMTS1). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7) indicating that additional rare variants remain to be identified.

Published
2018
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14. Correlation Between Macular Integrity Assessment and Optical Coherence Tomography Imaging of Ellipsoid Zone in Macular Telangiectasia Type 2

Author

Mukherjee, D, Lad, EM, Vann, RR, Jaffe, SJ, Clemons, TE, Friedlander, M, Chew, EY, Jaffe, GJ, Farsiu, S, Sahel, J-A, Guymer, R, Soubrane, G, Gaudric, A, Schwartz, S, Constable, I, Cooney, M, Egan, C, Singerman, L, Gillies, MC, Pauleikhoff, D, Moisseiev, J, Rosen, R, Murphy, R, Holz, F, Comer, G, Blodi, B, Do, D, Brucker, A, Narayanan, R, Wolf, S, Rosenfeld, P, Bernstein, PS, Miller, JW, Mukherjee, D, Lad, EM, Vann, RR, Jaffe, SJ, Clemons, TE, Friedlander, M, Chew, EY, Jaffe, GJ, Farsiu, S, Sahel, J-A, Guymer, R, Soubrane, G, Gaudric, A, Schwartz, S, Constable, I, Cooney, M, Egan, C, Singerman, L, Gillies, MC, Pauleikhoff, D, Moisseiev, J, Rosen, R, Murphy, R, Holz, F, Comer, G, Blodi, B, Do, D, Brucker, A, Narayanan, R, Wolf, S, Rosenfeld, P, Bernstein, PS, and Miller, JW

Abstract

PURPOSE: To correlate ellipsoid zone (EZ) defects on spectral-domain optical coherence tomography (SD-OCT) with retinal sensitivity loss on macular integrity assessment (MAIA) microperimetry in macular telangiectasia type 2 (MacTel). METHODS: Macular SD-OCT volumes and microperimetry maps were obtained during the international, multicenter, randomized phase 2 trial of ciliary neurotrophic factor for type 2 MacTel on two visits within 5 days of one another. Software was developed to register SD-OCT to MAIA scanning laser ophthalmoscopy images and to overlay EZ defect areas on the microperimetry maps generated from microperimetry sensitivity values at specific points and from interpolated sensitivity values. A total of 134 eyes of 67 patients were investigated. RESULTS: The semiautomated registration algorithm was found to be accurate, both qualitatively by visual inspection of the nearly perfect overlap of the retinal vessels and quantitatively as assessed by interobserver reliability metrics performed in 98 eyes of 49 patients (intraclass correlation of aggregate retinal sensitivity loss >0.99). Aggregate retinal sensitivity loss within the EZ defect area was highly correlated with EZ defect area (Pearson correlation coefficient 0.93 and 0.92 at screening and baseline for noninterpolated maps; both were 0.94 for interpolated maps; P values <0.001). CONCLUSIONS: With our software and image processing algorithms, there is nearly perfect correlation between retinal sensitivity on microperimetry and EZ defect area on SD-OCT. Our software allows determination of functional and structural changes with increasing disease severity and demonstrates that functional loss on microperimetry may be used as a surrogate marker of EZ loss on SD-OCT in type 2 MacTel.

Published
2017

16. Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS

Author

Smith BN, Ticozzi N, Fallini C, Gkazi AS, Topp S, Kenna KP, Scotter EL, Kost J, Keagle P, Miller JW, Calini D, Vance C, Danielson EW, Troakes C, Tiloca C, Al Sarraj S, Lewis EA, King A, Colombrita C, Pensato V, Castellotti B, de Belleroche J, Baas F, ten Asbroek AL, Sapp PC, McKenna Yasek D, McLaughlin RL, Polak M, Asress S, Esteban Pérez J, Muñoz Blanco JL, Simpson M, SLAGEN Consortium, van Rheenen W, Diekstra FP, Lauria G, Duga S, Corti S, Cereda C, Corrado L, Sorarù G, Morrison KE, Williams KL, Nicholson GA, Blair IP, Dion PA, Leblond CS, Rouleau GA, Hardiman O, Veldink JH, van den Berg LH, Al Chalabi A, Pall H, Shaw PJ, Turner MR, Talbot K, Taroni F, García Redondo A, Wu Z, Glass JD, Gellera C, Ratti A, Brown RH Jr, Silani V, Shaw CE, Landers JE, COMI , GIANCARLO, Smith, Bn, Ticozzi, N, Fallini, C, Gkazi, A, Topp, S, Kenna, Kp, Scotter, El, Kost, J, Keagle, P, Miller, Jw, Calini, D, Vance, C, Danielson, Ew, Troakes, C, Tiloca, C, Al Sarraj, S, Lewis, Ea, King, A, Colombrita, C, Pensato, V, Castellotti, B, de Belleroche, J, Baas, F, ten Asbroek, Al, Sapp, Pc, McKenna Yasek, D, Mclaughlin, Rl, Polak, M, Asress, S, Esteban Pérez, J, Muñoz Blanco, Jl, Simpson, M, Slagen, Consortium, van Rheenen, W, Diekstra, Fp, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Morrison, Ke, Williams, Kl, Nicholson, Ga, Blair, Ip, Dion, Pa, Leblond, C, Rouleau, Ga, Hardiman, O, Veldink, Jh, van den Berg, Lh, Al Chalabi, A, Pall, H, Shaw, Pj, Turner, Mr, Talbot, K, Taroni, F, García Redondo, A, Wu, Z, Glass, Jd, Gellera, C, Ratti, A, Brown RH, Jr, Silani, V, Comi, Giancarlo, Shaw, Ce, and Landers, Je

Published
2014

17. Genetic investigation of children with ataxia using exome sequencing

Author

FAWCETT K A, 17., A H, Nemeth, Schnekenberg, Rp, E M, Perkins, Miller, Jw, Davies, W, D'Adamo, Maria Cristina, Pessia, M, Sims, D, Gillard, E, Hudspith, K, Skehel, P, Williams, J, O'Regan, M, Jayawant, S, Jefferson, R, Hughes, S, Steinlin, M, Lustenberger, A, Ragoussis, J, Jackson, M, and S J, Tucker

Published
2016

18. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: Two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2

Author

Arnold J, Kilmartin D, Olson J, Neville S, Robinson K, Laird A, Richmond C, Farrow A, McKay S, McKechnie R, Evans G, Aaberg TM, Brower J, Waldron R, Loupe D, Gillman J, Myles B, Saperstein DA, Schachat AP, Bressler NM, Bressler SB, Nesbitt P, Porter T, Hawse P, Harnett M, Eager A, Belt J, Cain D, Emmert D, George T, Herring M, McDonald J, Mones J, Corcostegui B, Gilbert M, Duran N, Sisquella M, Nolla A, Margalef A, Miller JW, Gragoudas ES, Lane AM, Emmanuel N, Holbrook A, Evans C, Lord US, Walsh DK, Callahan CD, DuBois JL, Moy J, Kenney AG, Milde I, Platz ES, Lewis H, Kaiser PK, Holody LJ, Lesak E, Lichterman S, Siegel H, Fattori A, Ambrose G, Fecko T, Ross D, Burke S, Conway J, Singerman L, Zegarra H, Novak M, Bartel M, Tilocco DuBois K, Ilc M, Schura S, Joyce S, Tanner V, Rowe P, Smith Brewer S, Greanoff G, Daley G, DuBois J, Lehnhardt D, Kukula D, Fish GE, Jost BF, Anand R, Callanan D, Arceneaux S, Arnwine J, Ellenich P, King J, Aguado H, Rollins R, Anderson T, Nork C, Duignan K, Boleman B, Jurklies B, Pauleikhoff D, Hintzmann A, Fischer M, Sowa C, Behne E, Pournaras CJ, Donati G, Kapetanios AD, Cavaliere K, Guney Wagner S, Gerber N, Sickenberg M, Sickenberg V, Gans A, Hosner B, Sbressa A, Kozma C, Curchod M, Ardoni S, Harding S, Yang YC, Briggs M, Briggs S, Phil EB, Tompkin V, Jackson R, Pearson S, Natha S, Sharp J, Tompkin A, Lim JI, Flaxel C, Padilla M, Levin L, Walonker F, Cisneros L, Nichols T, Schmidt Erfurth U, Barbazetto I, Laqua H, Kupfer R, Bulow R, Glisovic B, Bredfeldt T, Elsner H, Wintzer V, Bahlmann D, Michels S, Gordes R, Neppert B, Grote M, Honnicke K, Blumenkranz MS, Little HL, Jack R, Espiritu LM, Unyi L, Regan J, Lamborn L, Silvestri C, Rosa RH, Rosenfeld PJ, Lewis ML, Rodriguez B, Torres A, Munoz N, Contreras T, Galvez M, Hess D, Cubillas T, Rams I, Slakter JS, Sorenson JA, Bruschi PA, Burke K, Schnipper E, Maranan L, Scolaro M, Riff M, Agresta E, Napoli J, Johansson I, Dedorsson I, Stenkula S, Hvarfner C, Carlsson T, Liljedahl AM, Fallstrom S, Jacobsson E, Hendeberg K, Soubrane G, Kuhn D, Oubraham H, Benelhani A, Kunsch A, Delhoste B, Ziverec G, Lasnier M, Debibie C, Lobes LA, Olsen K, Bahr BJ, Worstell NT, Wilcox LA, Wellman LA, Vagstad G, Steinberg D, Campbell A, Ma C, Dreyer R, Williamson B, Johnson M, Crider H, Anderson H, Brown T, Jelinek K, Graves D, Pope S, Boone R, Beaumont W, Margherio RR, Williams GA, Zajechowski M, Stanley C, Kulak M, Streasick P, Szdlowski L, Falk R, Shoichet S, Regan G, Manatrey P, Cumming K, Fadel R, Mitchel B, Vandell L, Yesestrepsky D, Medina T, Bridges C, Huston G, Koenig F, Benchaboune M, Mezmate K, Fontanay S, Meredith T, Binning J, Gualdoni J, Boyd L, Ort E, Barts B, Allen R, Dahl J, Holle T, Harvey PT, Kaus L, Leuschner D, Bolychuk S, Hewitt I, Voyce J, Menchini U, Virgili G, Lanzetta P, Ambesi M, Pirracchio A, Tedeschi M, Potter MJ, Sahota B, Hall L, Le G, Rai S, Johnson D, Stur M, Lukas J, Tittl M, Docker S, Vogl K, Pieramici DJ, Manos KS, Cooper R, Denbow RL, Lowery ER, Phillips DA, Thibeault SK, Tian Y, Alexander J, Orr PR, Black N, Escartin P, Hartley D, Haworth P, Hecker T, Hiscock D, Jamali F, Maradan N, North J, Norton B, Stapleton Hayes T, Taylor R, Huber G, Deslandes JY, Fsadni M, Hess I, de Pommerol H, Bobillier A, Reaves A, Banasik S, Birch R, Koester J, Stickles R, Truett K, McAlister L, Parker F, Strong HA, Azab M, Buskard N, Gray T, Manjuris U, Hao Y, Su XY, Mason M, Hynes L, Barbezetto I, Birngruber R, Flaxel CJ, Harvey P, Koester JM, Meredith TA, Murphy SA, Strong A, Ulrike M, Beck RW, Bird AC, Coscas G, Deutman A, Jampol L, Klein R, Maguire M, Rosenfeld P, Acreneaux S, Margherio RP, Staflin P, Mones JM, Schmidt Erfurth U., BANDELLO , FRANCESCO, Arnold, J, Kilmartin, D, Olson, J, Neville, S, Robinson, K, Laird, A, Richmond, C, Farrow, A, Mckay, S, Mckechnie, R, Evans, G, Aaberg, Tm, Brower, J, Waldron, R, Loupe, D, Gillman, J, Myles, B, Saperstein, Da, Schachat, Ap, Bressler, Nm, Bressler, Sb, Nesbitt, P, Porter, T, Hawse, P, Harnett, M, Eager, A, Belt, J, Cain, D, Emmert, D, George, T, Herring, M, Mcdonald, J, Mones, J, Corcostegui, B, Gilbert, M, Duran, N, Sisquella, M, Nolla, A, Margalef, A, Miller, Jw, Gragoudas, E, Lane, Am, Emmanuel, N, Holbrook, A, Evans, C, Lord, U, Walsh, Dk, Callahan, Cd, Dubois, Jl, Moy, J, Kenney, Ag, Milde, I, Platz, E, Lewis, H, Kaiser, Pk, Holody, Lj, Lesak, E, Lichterman, S, Siegel, H, Fattori, A, Ambrose, G, Fecko, T, Ross, D, Burke, S, Conway, J, Singerman, L, Zegarra, H, Novak, M, Bartel, M, Tilocco DuBois, K, Ilc, M, Schura, S, Joyce, S, Tanner, V, Rowe, P, Smith Brewer, S, Greanoff, G, Daley, G, Dubois, J, Lehnhardt, D, Kukula, D, Fish, Ge, Jost, Bf, Anand, R, Callanan, D, Arceneaux, S, Arnwine, J, Ellenich, P, King, J, Aguado, H, Rollins, R, Anderson, T, Nork, C, Duignan, K, Boleman, B, Jurklies, B, Pauleikhoff, D, Hintzmann, A, Fischer, M, Sowa, C, Behne, E, Pournaras, Cj, Donati, G, Kapetanios, Ad, Cavaliere, K, Guney Wagner, S, Gerber, N, Sickenberg, M, Sickenberg, V, Gans, A, Hosner, B, Sbressa, A, Kozma, C, Curchod, M, Ardoni, S, Harding, S, Yang, Yc, Briggs, M, Briggs, S, Phil, Eb, Tompkin, V, Jackson, R, Pearson, S, Natha, S, Sharp, J, Tompkin, A, Lim, Ji, Flaxel, C, Padilla, M, Levin, L, Walonker, F, Cisneros, L, Nichols, T, Schmidt Erfurth, U, Barbazetto, I, Laqua, H, Kupfer, R, Bulow, R, Glisovic, B, Bredfeldt, T, Elsner, H, Wintzer, V, Bahlmann, D, Michels, S, Gordes, R, Neppert, B, Grote, M, Honnicke, K, Blumenkranz, M, Little, Hl, Jack, R, Espiritu, Lm, Unyi, L, Regan, J, Lamborn, L, Silvestri, C, Rosa, Rh, Rosenfeld, Pj, Lewis, Ml, Rodriguez, B, Torres, A, Munoz, N, Contreras, T, Galvez, M, Hess, D, Cubillas, T, Rams, I, Slakter, J, Sorenson, Ja, Bruschi, Pa, Burke, K, Schnipper, E, Maranan, L, Scolaro, M, Riff, M, Agresta, E, Napoli, J, Johansson, I, Dedorsson, I, Stenkula, S, Hvarfner, C, Carlsson, T, Liljedahl, Am, Fallstrom, S, Jacobsson, E, Hendeberg, K, Soubrane, G, Kuhn, D, Oubraham, H, Benelhani, A, Kunsch, A, Delhoste, B, Ziverec, G, Lasnier, M, Debibie, C, Lobes, La, Olsen, K, Bahr, Bj, Worstell, Nt, Wilcox, La, Wellman, La, Vagstad, G, Steinberg, D, Campbell, A, Ma, C, Dreyer, R, Williamson, B, Johnson, M, Crider, H, Anderson, H, Brown, T, Jelinek, K, Graves, D, Pope, S, Boone, R, Beaumont, W, Margherio, Rr, Williams, Ga, Zajechowski, M, Stanley, C, Kulak, M, Streasick, P, Szdlowski, L, Falk, R, Shoichet, S, Regan, G, Manatrey, P, Cumming, K, Fadel, R, Mitchel, B, Vandell, L, Yesestrepsky, D, Medina, T, Bridges, C, Huston, G, Koenig, F, Benchaboune, M, Mezmate, K, Fontanay, S, Meredith, T, Binning, J, Gualdoni, J, Boyd, L, Ort, E, Barts, B, Allen, R, Dahl, J, Holle, T, Harvey, Pt, Kaus, L, Leuschner, D, Bolychuk, S, Hewitt, I, Voyce, J, Menchini, U, Bandello, Francesco, Virgili, G, Lanzetta, P, Ambesi, M, Pirracchio, A, Tedeschi, M, Potter, Mj, Sahota, B, Hall, L, Le, G, Rai, S, Johnson, D, Stur, M, Lukas, J, Tittl, M, Docker, S, Vogl, K, Pieramici, Dj, Manos, K, Cooper, R, Denbow, Rl, Lowery, Er, Phillips, Da, Thibeault, Sk, Tian, Y, Alexander, J, Orr, Pr, Black, N, Escartin, P, Hartley, D, Haworth, P, Hecker, T, Hiscock, D, Jamali, F, Maradan, N, North, J, Norton, B, Stapleton Hayes, T, Taylor, R, Huber, G, Deslandes, Jy, Fsadni, M, Hess, I, de Pommerol, H, Bobillier, A, Reaves, A, Banasik, S, Birch, R, Koester, J, Stickles, R, Truett, K, Mcalister, L, Parker, F, Strong, Ha, Azab, M, Buskard, N, Gray, T, Manjuris, U, Hao, Y, Su, Xy, Mason, M, Hynes, L, Barbezetto, I, Birngruber, R, Flaxel, Cj, Harvey, P, Koester, Jm, Meredith, Ta, Murphy, Sa, Strong, A, Ulrike, M, Beck, Rw, Bird, Ac, Coscas, G, Deutman, A, Jampol, L, Klein, R, Maguire, M, Rosenfeld, P, Acreneaux, S, Margherio, Rp, Staflin, P, Mones, Jm, and Schmidt Erfurth, U.

Abstract

PURPOSE: To determine if photodynamic therapy with verteporfin (Visudyne; Novartis AG, Bulach, Switzerland), termed verteporfin therapy, can safely reduce the risk of vision loss compared with a placebo (with sham treatment) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization, or with presumed early onset classic choroidal neovascularization with good visual acuity letter score, METHODS: This was a double-masked, placebo controlled (sham treatment), randomized, multicenter clinical trial involving 28 ophthalmology practices in Europe and North America. The study population was patients with age related macular degeneration, with subfoveal choroidal neovascularization lesions measuring no greater than 5400 mum in greatest linear dimension with either 1) occult with no classic choroidal neovascularization, best-corrected visual acuity score of at least 50 (Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent disease progression; or 2) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 (better than a Snellen equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) was administered by means of intravenous infusion of 30 mi over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 mum larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The main outcome measure was at least moderate vision loss, that is, a loss of at least 15 letters (approximately 3 lines), adhering to an intent-to treat analysis with the last observation carried forward to impute for missing data. RESULTS: Two hundred ten (93%) and 193 (86%) of the 225 patients in the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in the placebo group completed the month 12 and 24 examinations, respectively. On average, verteporfin-treated patients received five treatments over the 24 months of follow-up. The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination, although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group. Between the month 12 and 24 examinations, the treatment benefit grew so that by the month 24 examination, the vertepor-fin-treated eyes were less likely to have moderate or severe vision loss. Of the 225 verteporfin-treated patients, 121 (54%) compared with 76 (67%) of 114 placebo-treated patients lost at least 15 letters (P =.023). Likewise, 61 of the verteporfin-treated patients (30%) compared with 54 of the placebo-treated patients (47%) lost at least 30 letters (P = .001). Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization, This subgroup included 166 of the 225 verteporfin-treated patients (74%) and 92 of the 114 placebo-treated patients (81%). In these patients, 91 of the verteporfin-treated group (55%) compared with 63 of the placebo-treated group (68%) lost at least 15 letters (P =.032), whereas 48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group (47%) lost at least 30 letters (P =.004). Other secondary outcomes, including visual acuity letter score worse than 34 (approximate Snellen equivalent of 20/200 or worse), mean change in visual acuity letter score, development of classic choroidal neovascularization, progression of classic choroidal neovascularization and size of lesion, favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline. Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions (4 disc areas or less) or lower levels of visual acuity (letter score less than 65, an approximate Snellen equivalent of 20/50(-1) or worse) at baseline. Prospectively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit. Of the 123 verteporfin-treated patients and 64 placebo-heated patients with either visual acuity score Less than 65 or lesion size 4 disc areas or less at baseline, 60 (49%) and 48 (75%) lost at least 15 letters (P < .001), respectively, and 26 (21%) and 31 (48%) lost at least 30 letters (P 2001 by Elsevier Science Inc. All rights reserved.).

Published
2001

33. Recent trends in U.S. mammography use from 2000-2006: a population-based analysis.

Author

Ryerson AB, Miller JW, Eheman CR, Leadbetter S, and White MC

Abstract

OBJECTIVE: We previously reported a decrease in regular mammogram use from 2000 through 2005. To determine whether a downward trend continued in 2006 we re-examined mammography utilization reported in Behavioral Risk Factor Surveillance System data from 2000 through 2006. METHODS: Age-adjusted percentages of women who reported having had a mammogram in the past 2 years were estimated by demographic and socioeconomic characteristics. Logistic regression was used to assess the linear time trends. RESULTS: The total age-adjusted proportion of all women aged > or =40 years who reported having had a mammogram within the 2 preceding years did not change when comparing data from 2000 (76.5% [95% CI: 75.9-77.0]) to 2006 (76.1% [75.7-76.6]). However, among those with health care coverage, a statistically significant decline in utilization occurred among women age 40 through 59 years, and non-Hispanic white women. CONCLUSIONS: A substantial proportion of women are not being screened by mammography as recommended. Recent data suggest that patterns of utilization have leveled off or declined among certain subgroups of women. These data underscore the need to more effectively address current barriers to the utilization of mammography. Copyright © 2008 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Published
2008
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35. Reinforcing the divide: the influence of the U.S. Census on American identity development.

Author

Miller JW Jr.

Abstract

Accounts of race in the United States have traditionally been steeped in prejudicial notions consistent with the society (Lusane, 2000; U.S. Census Bureau, 2000; Griffin, Caplinger, Lively, Malcom, McDaniel, & Nelsen, 1997). The U.S. Census has been used as an instrument in the continued dichotomous division of American citizens into either one of two groups, Whites and Nonwhites (Ngai, 1999). This essay examines the impact of the U.S. Census on U.S. law, public policy, and distribution of privilege between Whites and Nonwhites. This essay also addresses the influence of census-based racial classification on social work practice and education. [ABSTRACT FROM AUTHOR]

Published
2007
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41. The newer antiepileptic drugs: their collective role and defining characteristics.

Author

Anderson GD and Miller JW

Abstract

The utility of long-established antiepileptic drugs (AEDs) has been restricted by lack of efficacy in some patients, neurotoxicity, teratogenicity, idiosyncratic reactions, and complex pharmacokinetics. Eight new AEDs have been introduced in the United States since 1993 (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, zonisamide). These newer AEDs offer both options for improved efficacy in the treatment of refractory seizures and the possibility of reducing or eliminating the adverse effects of older AEDs. Some of the newer AEDs are associated with less sedation, less weight gain, and possibly fewer endocrine effects. Moreover, the newer agents' fewer drug interactions offer greater ease of use. While the current role of the newer AEDs generally remains limited to second-line therapy, the many new options they have afforded clinicians are of considerable value, given the great variability of patient response to AED therapy. Because of this variability and the lack of data directly comparing the newer AEDs with one another, all of the newer AEDs should be available to patients. [ABSTRACT FROM AUTHOR]

Published
2001

43. B??K??SY AUDIOMETRY: DEMONSTRATION OF INTERRUPTED TONE TEMPORARY THRESHOLD SHIFT

Author

Miller Jw, D T Cody, and Griffing T

Subjects
Adult, Male, Brain Diseases, medicine.medical_specialty, Multiple Sclerosis, Bekesy audiometry, business.industry, Auditory Threshold, Audiology, Neurologic Manifestations, Tone (musical instrument), Audiometry, Otorhinolaryngology, Methods, Humans, Medicine, Female, business, Bone Conduction, Hearing Disorders, Auditory fatigue
Published
1969

48. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin - 1-year results of a randomized clinical trial - VIP report no. 1

Author

Arnold J, Kilmartin D, Olson J, Neville S, Robinson K, Laird A, Richmond C, Farrow A, McKay S, Saperstein DA, Aaberg TM, Johnson JB, Waldron R, Loupe D, Gillman J, Myles B, Schachat AP, Bressler NM, Bressler SB, Nesbitt P, Porter T, Hawse P, Hartnett M, Eager A, Belt J, Cain D, Emmert D, George T, Herring M, McDonald J, Mones J, Corcostegui B, Gilbert M, Duran N, Sisquella M, Nolla A, Margalef A, Miller JW, Gragoudas ES, Lane AM, Emmanuel N, Holbrook A, Evans C, Lord US, Walsh DK, Callahan CD, DuBois JL, Lewis H, Kaiser PK, Holody LJ, Lesak E, Lichterman S, Siegel H, Fattori A, Ambrose G, Fecko T, Ross D, Burke S, Singerman L, Zegarra H, Novak M, Bartel M, Tilocco DuBois K, Iic M, Schura S, Mayes SJ, Tanner V, Rowe P, Smith Brewer S, Kukula D, Greanoff G, Daley G, DuBois J, Lehnhardt D, Fish GE, Jost BF, Anand R, Callanan D, Arceneaux S, Arnwine J, Ellenich P, King J, Aguado H, Rollins R, Jurklies B, Pauleikhoff D, Hintzmann A, Fischer M, Sowa C, Behne E, Pournaras CJ, Donati G, Kapetanios AD, Cavaliere K, Guney Wagner S, Gerber N, Sickenberg M, Sickenberg V, Gans A, Hosner B, Sbressa A, Kozma C, Curchod M, Cancelli SA, Harding S, Yang YC, Briggs M, Briggs S, Tompkin V, Jackson R, Pearson S, Natha S, Sharp J, Lim JI, Flaxel C, Padilla M, Levin L, Walonker F, Cisneros L, Nichols T, Schmidt Erfurth U, Barbazetto I, Laqua H, Kupfer R, Bulow R, Glisovic B, Bredfeldt T, Elsner H, Wintzer V, Bahlmann D, Michels S, Blumenkranz MS, Little HL, Jack R, Espiritu LM, Unyi L, Regan J, Lamborn L, Silvestri C, Rosa RH, Rosenfeld PJ, Lewis ML, Rodriguez B, Torres A, Munoz N, Contreras T, Galvez M, Hess D, Cubillas T, Rams I, Slakter JS, Sorenson JA, Bruschi PA, Burke K, Schnipper E, Maranan L, Scolaro M, Riff M, Agresta E, Johansson I, Dedorsson I, Stenkula S, Hvarfner C, Carlsson T, Liljedahl AM, Fallstrom S, Jacobsson E, Soubrane G, Kuhn D, Oubraham H, Benelhani A, Kunsch A, Delhoste B, Ziverec G, Lasnier M, Lobes LA, Olsen K, Bahr BJ, Worstell NT, Wilcox LA, Wellman LA, Vagstad G, Steinberg D, Campbell A, Dreyer R, Williamson B, Johnson M, Crider H, Margherio RR, Williams GA, Zajechowski M, Stanley C, Kulak M, Streasick P, Szdlowski L, Falk R, Shoichet S, Regan G, Manatrey P, Cumming K, Koenig F, Benchaboune M, Mezmate K, Fontanay S, Meredith T, Binning J, Gualdoni J, Boyd L, Ort E, Barts B, Allen R, Dahl J, Holle T, Harvey PT, Kaus L, Leuschner D, Bolychuk S, Hewitt I, Menchini U, Virgili G, Lanzetta P, Ambesi M, Pirracchio A, Tedeschi M, Potter MJ, Sahota B, Hall L, Stur M, Lukas J, Tittl M, Docker S, Vogl K, Pieramici DJ, Manos KS, Cooper R, Denbow RL, Lowery ER, Phillips DA, Thibeault SK, Tian Y, Harnett M, Black N, Escartin P, Hartley D, Haworth P, Hecker T, Hiscock D, Jamali F, Maradan N, North J, Norton B, Stapleton Hayes T, Taylor R, Huber G, Deslandes JY, Fsadni M, Hess I, de Pommerol H, Bobillier A, Reaves A, Banasik S, Koester J, Gray T, Truett K, Baker J, McAlister L, Birch R, Strong A, Azab M, Buskard N, Manjuris U, Hao Y, Mason M, McCurry U, Birngruber R, Harvey P, Koester JM, Ma C, Murphy SA, Soubrane S, Strong HA, van den Berg H, Beck RW, Bird AC, Coscas G, Deutman A, Jampol L, Klein R, Maguire M, Rosenfeld P, Margherio RP, Staflin P., BANDELLO , FRANCESCO, Arnold, J, Kilmartin, D, Olson, J, Neville, S, Robinson, K, Laird, A, Richmond, C, Farrow, A, Mckay, S, Saperstein, Da, Aaberg, Tm, Johnson, Jb, Waldron, R, Loupe, D, Gillman, J, Myles, B, Schachat, Ap, Bressler, Nm, Bressler, Sb, Nesbitt, P, Porter, T, Hawse, P, Hartnett, M, Eager, A, Belt, J, Cain, D, Emmert, D, George, T, Herring, M, Mcdonald, J, Mones, J, Corcostegui, B, Gilbert, M, Duran, N, Sisquella, M, Nolla, A, Margalef, A, Miller, Jw, Gragoudas, E, Lane, Am, Emmanuel, N, Holbrook, A, Evans, C, Lord, U, Walsh, Dk, Callahan, Cd, Dubois, Jl, Lewis, H, Kaiser, Pk, Holody, Lj, Lesak, E, Lichterman, S, Siegel, H, Fattori, A, Ambrose, G, Fecko, T, Ross, D, Burke, S, Singerman, L, Zegarra, H, Novak, M, Bartel, M, Tilocco DuBois, K, Iic, M, Schura, S, Mayes, Sj, Tanner, V, Rowe, P, Smith Brewer, S, Kukula, D, Greanoff, G, Daley, G, Dubois, J, Lehnhardt, D, Fish, Ge, Jost, Bf, Anand, R, Callanan, D, Arceneaux, S, Arnwine, J, Ellenich, P, King, J, Aguado, H, Rollins, R, Jurklies, B, Pauleikhoff, D, Hintzmann, A, Fischer, M, Sowa, C, Behne, E, Pournaras, Cj, Donati, G, Kapetanios, Ad, Cavaliere, K, Guney Wagner, S, Gerber, N, Sickenberg, M, Sickenberg, V, Gans, A, Hosner, B, Sbressa, A, Kozma, C, Curchod, M, Cancelli, Sa, Harding, S, Yang, Yc, Briggs, M, Briggs, S, Tompkin, V, Jackson, R, Pearson, S, Natha, S, Sharp, J, Lim, Ji, Flaxel, C, Padilla, M, Levin, L, Walonker, F, Cisneros, L, Nichols, T, Schmidt Erfurth, U, Barbazetto, I, Laqua, H, Kupfer, R, Bulow, R, Glisovic, B, Bredfeldt, T, Elsner, H, Wintzer, V, Bahlmann, D, Michels, S, Blumenkranz, M, Little, Hl, Jack, R, Espiritu, Lm, Unyi, L, Regan, J, Lamborn, L, Silvestri, C, Rosa, Rh, Rosenfeld, Pj, Lewis, Ml, Rodriguez, B, Torres, A, Munoz, N, Contreras, T, Galvez, M, Hess, D, Cubillas, T, Rams, I, Slakter, J, Sorenson, Ja, Bruschi, Pa, Burke, K, Schnipper, E, Maranan, L, Scolaro, M, Riff, M, Agresta, E, Johansson, I, Dedorsson, I, Stenkula, S, Hvarfner, C, Carlsson, T, Liljedahl, Am, Fallstrom, S, Jacobsson, E, Soubrane, G, Kuhn, D, Oubraham, H, Benelhani, A, Kunsch, A, Delhoste, B, Ziverec, G, Lasnier, M, Lobes, La, Olsen, K, Bahr, Bj, Worstell, Nt, Wilcox, La, Wellman, La, Vagstad, G, Steinberg, D, Campbell, A, Dreyer, R, Williamson, B, Johnson, M, Crider, H, Margherio, Rr, Williams, Ga, Zajechowski, M, Stanley, C, Kulak, M, Streasick, P, Szdlowski, L, Falk, R, Shoichet, S, Regan, G, Manatrey, P, Cumming, K, Koenig, F, Benchaboune, M, Mezmate, K, Fontanay, S, Meredith, T, Binning, J, Gualdoni, J, Boyd, L, Ort, E, Barts, B, Allen, R, Dahl, J, Holle, T, Harvey, Pt, Kaus, L, Leuschner, D, Bolychuk, S, Hewitt, I, Menchini, U, Bandello, Francesco, Virgili, G, Lanzetta, P, Ambesi, M, Pirracchio, A, Tedeschi, M, Potter, Mj, Sahota, B, Hall, L, Stur, M, Lukas, J, 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Subjects
Photomedicine group
Abstract

Objective: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (m and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better. Intervention: Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water, n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000 mum larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present. Main Outcome Measures: The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis. Results: At baseline, move than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least five letters (1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01), Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment. Conclusions: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients. Ophthalmology 2001; 108:841-852 (C) 2001 by the American Academy of Ophthalmology.

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