Literature DB >> 33406961

Clinical trial design for neuroprotection in RHO autosomal dominant retinitis pigmentosa; outcome measure considerations.

Benjamin Otte1, Chris Andrews1, Gabrielle Lacy1, Kari Branham1, David C Musch1,2, Kanishka T Jayasundera1.   

Abstract

Purpose: To identify structural and functional outcome measures among patients with Rho-positive autosomal dominant Retinitis Pigmentosa (adRP) to aid neuroprotection trial design.
Methods: This was a retrospective cohort study of 52 patients with Rho-positive adRP. We measured Goldmann Visual Fields (GVF) constriction in four sectors (nasal, temporal, inferior, superior), and sectoral Ellipsoid Zone (EZ) width degeneration using Spectral Domain Optical Coherence Tomography (OCT) scans. Disease progression trajectories were projected using mixed effects modeling.
Results: Superior GVF was most constricted at presentation and had the shallowest trajectory (less steep negative slope); Inferior GVF was less constricted (corrected p < .001) and had a steeper negative slope (corrected p = .019) than superior GVF. Temporal EZ was most stable on OCT with a relatively shallow negative trajectory (corrected p = .011).Conclusions: Patients' superior visual fields presented with more constriction and subsequently had a shallow negative slope suggesting the corresponding inferior retina may be "burned out" at presentation. Targeted therapies for adRP will likely show a greater efficacy signal if delivered to the superior and nasal retina, which may demonstrate more change on OCT and GVF over the course of a neuroprotection trial.Translational Relevance: Mixed effects analysis of sectoral visual field constriction and EZ degeneration in Rho-positive adRP can prove useful in monitoring therapeutic efficacy and identifying targets for local therapies.

Entities:  

Keywords:  Autosomal Dominant Retinitis Pigmentosa; Ellipsoid zone; Goldmann Visual Field; Optical Coherence Tomography; mixed effects; neuroprotection; retinal degeneration; rhodopsin

Mesh:

Substances:

Year:  2021        PMID: 33406961      PMCID: PMC7987885          DOI: 10.1080/13816810.2020.1867752

Source DB:  PubMed          Journal:  Ophthalmic Genet        ISSN: 1381-6810            Impact factor:   1.803


  29 in total

1.  Classification of disease severity in retinitis pigmentosa.

Authors:  Mustafa Iftikhar; Marili Lemus; Bushra Usmani; Peter A Campochiaro; José Alain Sahel; Hendrik P N Scholl; Syed Mahmood Ali Shah
Journal:  Br J Ophthalmol       Date:  2019-01-31       Impact factor: 4.638

2.  Correlation between Visual Function and Structural Characteristics of the Macula in Advanced Retinitis Pigmentosa.

Authors:  Gisung Son; Suhwan Lee; Yoon Jeon Kim; Joo Yong Lee; June-Gone Kim; Young Hee Yoon
Journal:  Ophthalmologica       Date:  2019-03-20       Impact factor: 3.250

3.  Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa.

Authors:  T P Dryja; T L McGee; L B Hahn; G S Cowley; J E Olsson; E Reichel; M A Sandberg; E L Berson
Journal:  N Engl J Med       Date:  1990-11-08       Impact factor: 91.245

4.  Effect of stimulus size on static visual fields in patients with retinitis pigmentosa.

Authors:  W H Swanson; J Felius; D G Birch
Journal:  Ophthalmology       Date:  2000-10       Impact factor: 12.079

5.  Two forms of autosomal dominant primary retinitis pigmentosa.

Authors:  R W Massof; D Finkelstein
Journal:  Doc Ophthalmol       Date:  1981-11       Impact factor: 2.379

6.  Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man.

Authors:  A V Cideciyan; D C Hood; Y Huang; E Banin; Z Y Li; E M Stone; A H Milam; S G Jacobson
Journal:  Proc Natl Acad Sci U S A       Date:  1998-06-09       Impact factor: 11.205

7.  Retrospective Analysis of Structural Disease Progression in Retinitis Pigmentosa Utilizing Multimodal Imaging.

Authors:  Thiago Cabral; Jesse D Sengillo; Jimmy K Duong; Sally Justus; Katherine Boudreault; Kaspar Schuerch; Rubens Belfort; Vinit B Mahajan; Janet R Sparrow; Stephen H Tsang
Journal:  Sci Rep       Date:  2017-09-04       Impact factor: 4.379

8.  Intraobserver Repeatability and Interobserver Reproducibility of Ellipsoid Zone Measurements in Retinitis Pigmentosa.

Authors:  Margaret R Strampe; Alison L Huckenpahler; Brian P Higgins; Sergey Tarima; Alexis Visotcky; Kimberly E Stepien; Christine N Kay; Joseph Carroll
Journal:  Transl Vis Sci Technol       Date:  2018-06-04       Impact factor: 3.283

9.  Natural History Study of Retinal Structure, Progression, and Symmetry Using Ellipzoid Zone Metrics in RPGR-Associated Retinopathy.

Authors:  James J L Tee; Yesa Yang; Angelos Kalitzeos; Andrew Webster; James Bainbridge; Michel Michaelides
Journal:  Am J Ophthalmol       Date:  2018-10-09       Impact factor: 5.258

10.  In vivo Editing of the Human Mutant Rhodopsin Gene by Electroporation of Plasmid-based CRISPR/Cas9 in the Mouse Retina.

Authors:  Maria Carmela Latella; Maria Teresa Di Salvo; Fabienne Cocchiarella; Daniela Benati; Giulia Grisendi; Antonella Comitato; Valeria Marigo; Alessandra Recchia
Journal:  Mol Ther Nucleic Acids       Date:  2016-11-22       Impact factor: 10.183

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