Pseudo-fovea formation after gene therapy for RPE65- LCA

Investigative Ophthalmology and Visual Science

Volumn 56, Issue 1, 2015, Pages 526-537

  Cideciyan, Artur V ^a   Aguirre, Geoffrey K ^b   Jacobson, Samuel G ^a   Butt, Omar H ^b   Schwartz, Sharon B ^a   Swider, Malgorzata ^a   Roman, Alejandro J ^a   Sadigh, Sam ^a   Hauswirth, William W ^c  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

Author keywords

Gene therapy; Nystagmus; Retinal degeneration

Indexed keywords

PEPTIDES AND PROTEINS; RETINAL PIGMENT EPITHELIUM SPECIFIC PROTEIN 65KDA; UNCLASSIFIED DRUG; CIS TRANS ISOMERASE; DNA; RETINOID ISOMEROHYDROLASE;

ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; EYE FIXATION; EYE MOVEMENT CONTROL; FUNCTIONAL MAGNETIC RESONANCE IMAGING; GENE THERAPY; HUMAN; HUMAN TISSUE; INFRARED RADIATION; LEBER CONGENITAL AMAUROSIS; NYSTAGMUS; OPTICAL COHERENCE TOMOGRAPHY; PRIORITY JOURNAL; PSEUDO FOVEA; RETINA DISEASE; VISUAL ACUITY; VISUAL FEEDBACK; VISUAL FIELD; VISUAL STIMULATION; VISUAL THRESHOLD; ADULT; CLINICAL TRIAL; EYE MOVEMENT; FEMALE; FOLLOW UP; GENETICS; MALE; METABOLISM; MIDDLE AGED; MUTATION; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEOTIDE SEQUENCE; PATHOLOGY; PHASE 1 CLINICAL TRIAL; PROCEDURES; RANDOMIZED CONTROLLED TRIAL; RETINA FOVEA; TREATMENT OUTCOME;

ADULT; CIS-TRANS-ISOMERASES; DNA; DNA MUTATIONAL ANALYSIS; EYE MOVEMENTS; FEMALE; FOLLOW-UP STUDIES; FOVEA CENTRALIS; GENETIC THERAPY; HUMANS; LEBER CONGENITAL AMAUROSIS; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; MUTATION; TREATMENT OUTCOME; VISUAL ACUITY;

EID: 84921783225     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.14-15895     Document Type: Article

References (57)

1. Putnam NM, Hofer HJ, Doble N, Chen L, Carroll J, Williams DR. The locus of fixation and the foveal cone mosaic. J Vis. 2005; 5(7):632–639.
2. Wurtz RH. Neuronal mechanisms of visual stability. Vision Res. 2008;48:2070–2089.
3. Rossi EA, Roorda A. The relationship between visual resolution and cone spacing in the human fovea. Nat Neurosci. 2010;13: 156–157.
4. Kowler E. Eye movements: the past 25 years. Vision Res. 2011; 51:1457–1483.
5. Weiss AH, Biersdorf WR. Visual sensory disorders in congenital nystagmus. Ophthalmology. 1989;96:517–523.
6. Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med. 2008;358:2231–2239.
7. Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358:2240–2248.
8. Hauswirth WW, Aleman TS, Kaushal S, et al. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther. 2008;19: 979–990.
9. Cideciyan AV, Aleman TS, Boye SL, et al. Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proc Natl Acad Sci U S A. 2008;105:15112–15117.
10. Maguire AM, High KA, Auricchio A, et al. Age-dependent effects of RPE65 gene therapy for Leber’s congenital amaurosis: a phase 1 dose-escalation trial. Lancet. 2009;374:1597–1605.
11. Jacobson SG, Cideciyan AV, Ratnakaram R, et al. Gene therapy for Leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Arch Ophthalmol. 2012;130:9–24.
12. Cideciyan AV, Hauswirth WW, Aleman TS, et al. Vision 1 year after gene therapy for Leber’s congenital amaurosis. N Engl J Med. 2009;361:725–727.
13. Cideciyan AV, Hauswirth WW, Aleman TS, et al. Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year. Hum Gene Ther. 2009;20:999–1004.
14. Cideciyan AV, Jacobson SG, Beltran WA, et al. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proc Natl Acad Sci U S A. 2013;110:E517–E525.
15. Jacobson SG, Aleman TS, Cideciyan AV, et al. Human cone photoreceptor dependence on RPE65 isomerase. Proc Natl Acad Sci U S A. 2007;104:15123–15128.
16. Cideciyan AV, Swider M, Aleman TS, et al. Macular function in macular degenerations: repeatability of microperimetry as a potential outcome measure for ABCA4-associated retinopathy trials. Invest Ophthalmol Vis Sci. 2012;53:841–852.
17. Ferris FL III, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol. 1982;94: 91–96.
18. Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis: I. Segmentation and surface reconstruction. Neuroimage. 1999; 9:179–194.
19. Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A. 2000;97:11050–11055.
20. Fischl B, Sereno MI, Tootell RB, Dale AM. High-resolution intersubject averaging and a coordinate system for the cortical surface. Hum Brain Mapp. 1999;8:272–284.
21. Greve DN, Van der Haegen L, Cai Q, et al. A surface-based analysis of language lateralization and cortical asymmetry. J Cogn Neurosci. 2013;25:1477–1492.
22. Aguirre GK, Zarahn E, D’Esposito M. The variability of human, BOLD hemodynamic responses. Neuroimage. 1998;8:360–369.
23. Benson NC, Butt OH, Datta R, Radoeva PD, Brainard DH, Aguirre GK. The retinotopic organization of striate cortex is well predicted by surface topology. Curr Biol. 2012;22:2081–2085.
24. Benson NC, Butt OH, Brainard DH, Aguirre GK. Correction of distortion in flattened representations of the cortical surface allows prediction of V1-V3 functional organization from anatomy. PLoS Comput Biol. 2014;10:e1003538.
25. Jacobson SG, Cideciyan AV, Aleman TS, et al. RDH12 and RPE65, visual cycle genes causing Leber congenital amaurosis, differ in disease expression. Invest Ophthalmol Vis Sci. 2007; 48:332–338.
26. Maeda T, Cideciyan AV, Maeda A, et al. Loss of cone photoreceptors caused by chromophore depletion is partially prevented by the artificial chromophore pro-drug, 9-cis-retinyl acetate. Hum Mol Genet. 2009;18:2277–2287.
27. Paunescu K, Wabbels B, Preising MN, Lorenz B. Longitudinal and cross-sectional study of patients with early-onset severe retinal dystrophy associated with RPE65 mutations. Graefes Arch Clin Exp Ophthalmol. 2005;243:417–426.
28. Lorenz B, Poliakov E, Schambeck M, Friedburg C, Preising MN, Redmond TM. A comprehensive clinical and biochemical functional study of a novel RPE65 hypomorphic mutation. Invest Ophthalmol Vis Sci. 2008;49:5235–5242.
29. Walia S, Fishman GA, Jacobson SG, et al. Visual acuity in patients with Leber’s congenital amaurosis and early childhood- onset retinitis pigmentosa. Ophthalmology. 2010;117: 1190–1198.
30. Weleber RG, Michaelides M, Trzupek KM, Stover NB, Stone EM. The phenotype of severe early childhood onset retinal dystrophy (SECORD) from mutation of RPE65 and differentiation from Leber congenital amaurosis. Invest Ophthalmol Vis Sci. 2011;52:292–302.
31. Roman AJ, Cideciyan AV, Schwartz SB, Olivares MB, Heon E, Jacobson SG. Intervisit variability of visual parameters in Leber congenital amaurosis caused by RPE65 mutations. Invest Ophthalmol Vis Sci. 2013;54:1378–1383.
32. Abadi RV, Scallan CJ. Waveform characteristics of manifest latent nystagmus. Invest Ophthalmol Vis Sci. 2000;41:3805–3817.
33. Wiggins D, Woodhouse JM, Margrain TH, Harris CM, Erichsen JT. Infantile nystagmus adapts to visual demand. Invest Ophthalmol Vis Sci. 2007;48:2089–2094.
34. Sunness JS, Liu T, Yantis S. Retinotopic mapping of the visual cortex using functional magnetic resonance imaging in a patient with central scotomas from atrophic macular degeneration. Ophthalmology. 2004;111:1595–1598.
35. Leigh RJ, Zee DS. Eye movements of the blind. Invest Ophthalmol Vis Sci. 1980;19:328–331.
36. Hall EC, Gordon J, Hainline L, Abramov I, Engber K. Childhood visual experience affects adult voluntary ocular motor control. Optom Vis Sci. 2000;77:511–523.
37. Hall EC, Gordon J, Abel LA, Hainline L, Abramov I. Nystagmus waveforms in blindness. Vis Impair Res. 2000;2:65–73.
38. Jacobson SG, Aleman TS, Cideciyan AV, et al. Identifying photoreceptors in blind eyes caused by RPE65 mutations: prerequisite for human gene therapy success. Proc Natl Acad Sci U S A. 2005;102:6177–6182.
39. Jacobson SG, Cideciyan AV, Aleman TS, et al. Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations. Invest Ophthalmol Vis Sci. 2008; 49:4573–4577.
40. Cham KM, Anderson AJ, Abel LA. Oscillopsia and the influence of stress and motivation in fusion maldevelopment nystagmus syndrome. Invest Ophthalmol Vis Sci. 2013;54:2004–2010.
41. Jones PH, Harris CM, Woodhouse JM, Margrain TH, Ennis FA, Erichsen JT. Stress and visual function in infantile nystagmus syndrome. Invest Ophthalmol Vis Sci. 2013;54:7943–7951.
42. Nau A, Hertle RW, Yang D. Effect of tongue stimulation on nystagmus eye movements in blind patients. Brain Struct Funct. 2012;217:761–765.
43. Beh SC, Tehrani AS, Kheradmand A, Zee DS. Damping of monocular pendular nystagmus with vibration in a patient with multiple sclerosis. Neurology. 2014;82:1380–1381.
44. Jacobson SG, Aleman TS, Cideciyan AV, et al. Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations. Invest Ophthalmol Vis Sci. 2009;50:2368–2375.
45. Simonelli F, Maguire AM, Testa F, et al. Gene therapy for Leber’s congenital amaurosis is safe and effective through 1.5 years after vector administration. Mol Ther. 2010;18:643–650.
46. Testa F, Maguire AM, Rossi S, et al. Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2. Ophthalmology. 2013;120:1283–1291.
47. Coogan TA, Van Essen DC. Development of connections within and between areas V1 and V2 of macaque monkey. J Comp Neurol. 1996;372:327–342.
48. Butt OH, Benson NC, Datta R, Aguirre GK. The fine-scale functional connectivity of striate cortex in sighted and blind people. J Neurosci. 2013;33:16209–16219.
49. Aguirre GK, Kom´aromy AM, Cideciyan AV, et al. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation. PLoS Med. 2007;4:e230.
50. Bennett J, Ashtari M, Wellman J, et al. AAV2 gene therapy readministration in three adults with congenital blindness. Sci Transl Med. 2012;4:120ra15.
51. Ashtari M, Cyckowski LL, Monroe JF, et al. The human visual cortex responds to gene therapy-mediated recovery of retinal function. J Clin Invest. 2011;121:2160–2168.
52. Koenekoop RK, Sui R, Sallum J, et al. Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial. Lancet. 2014;348:1513–1520.
53. Timberlake GT, Mainster MA, Peli E, Augliere RA, Essock EA, Arend LE. Reading with a macular scotoma. I. Retinal location of scotoma and fixation area. Invest Ophthalmol Vis Sci. 1986; 27:1137–1147.
54. Baker CI, Peli E, Knouf N, Kanwisher NG. Reorganization of visual processing in macular degeneration. J Neurosci. 2005; 25:614–618.
55. Dilks DD, Baker CI, Peli E, Kanwisher N. Reorganization of visual processing in macular degeneration is not specific to the ‘‘preferred retinal locus.’’ J Neurosci. 2009;29:2768–2773.
56. Baker CI, Dilks DD, Peli E, Kanwisher N. Reorganization of visual processing in macular degeneration: replication and clues about the role of foveal loss. Vision Res. 2008;48:1910–1919.
57. Dilks DD, Julian JB, Peli E, Kanwisher N. Reorganization of visual processing in age-related macular degeneration depends on foveal loss. Optom Vis Sci. 2014;91:e199–206.