Literature DB >> 26448901

Outer Segment Thickness Predicts Visual Field Response to QLT091001 in Patients with RPE65 or LRAT Mutations.

Yuquan Wen1, David G Birch2.   

Abstract

PURPOSE: To determine whether the degree of change in Goldmann visual fields (GVFs) following oral administration of QLT091001 was related to baseline measures of retinal structure.
METHODS: Oral QLT091001 was administered once daily for 7 days in all study patients. Comprehensive ophthalmic testing, including spectral-domain optical coherence tomography (SD-OCT), was conducted in 14 patients with Leber congenital amaurosis (LCA) and 18 patients with retinitis pigmentosa (RP) at seven international sites. Average thickness of the outer segment (OS) layer was calculated over central 20°. Both eyes of each subject were evaluated separately.
RESULTS: Nineteen of 28 eyes (68%) with LCA and 13 of 36 eyes (36%) with RP responded to QLT091001. Among these responders, the average baseline thickness of the OS layer (central 20°) was 13.5 μm in the LCA cohort and 11.7 μm in the RP cohort. Nonresponders had average baseline OS thickness of less than 4.6 μm in both cohorts. The OS thickness in the central 20° was significantly shorter in nonresponders than responders in the LCA cohort (P = 0.01, t-test) and in the RP cohort (P = 0.02, Wilcoxon rank sum test). The OS thickness in the central 20° did not change significantly from baseline during the first 2 months (P = 0.09, t-test, paired).
CONCLUSIONS: The present findings suggest that there is a close parallel between the thickness of the photoreceptor layer and the potential for functional improvement in these patients. TRANSLATIONAL RELEVANCE: SD-OCT thickness in the central retina may be useful for predicting the visual field response in the peripheral retina to QLT091001. (https://clinicaltrials.gov/ct2/show/NCT01014052 number, NCT01014052).

Entities:  

Keywords:  Leber congenital amaurosis; clinical trial; layer thickness; retinal degeneration; retinitis pigmentosa; segmentation; spectral-domain optical coherence tomography; visual fields

Year:  2015        PMID: 26448901      PMCID: PMC4594504          DOI: 10.1167/tvst.4.5.8

Source DB:  PubMed          Journal:  Transl Vis Sci Technol        ISSN: 2164-2591            Impact factor:   3.283


  33 in total

1.  RPE65 is the isomerohydrolase in the retinoid visual cycle.

Authors:  Gennadiy Moiseyev; Ying Chen; Yusuke Takahashi; Bill X Wu; Jian-Xing Ma
Journal:  Proc Natl Acad Sci U S A       Date:  2005-08-22       Impact factor: 11.205

2.  Mislocalized opsin and cAMP signaling: a mechanism for sprouting by rod cells in retinal degeneration.

Authors:  Jianfeng Wang; Nan Zhang; Annie Beuve; Ellen Townes-Anderson
Journal:  Invest Ophthalmol Vis Sci       Date:  2012-09-19       Impact factor: 4.799

3.  Rod sensitivity, cone sensitivity, and photoreceptor layer thickness in retinal degenerative diseases.

Authors:  David G Birch; Yuquan Wen; Kelly Locke; Donald C Hood
Journal:  Invest Ophthalmol Vis Sci       Date:  2011-09-09       Impact factor: 4.799

4.  Mutations in the gene encoding lecithin retinol acyltransferase are associated with early-onset severe retinal dystrophy.

Authors:  D A Thompson; Y Li; C L McHenry; T J Carlson; X Ding; P A Sieving; E Apfelstedt-Sylla; A Gal
Journal:  Nat Genet       Date:  2001-06       Impact factor: 38.330

5.  Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.

Authors:  H Morimura; G A Fishman; S A Grover; A B Fulton; E L Berson; T P Dryja
Journal:  Proc Natl Acad Sci U S A       Date:  1998-03-17       Impact factor: 11.205

6.  Rod photoreceptor neurite sprouting in retinitis pigmentosa.

Authors:  Z Y Li; I J Kljavin; A H Milam
Journal:  J Neurosci       Date:  1995-08       Impact factor: 6.167

7.  Relationship between retinal layer thickness and the visual field in early age-related macular degeneration.

Authors:  Jennifer H Acton; R Theodore Smith; Donald C Hood; Vivienne C Greenstein
Journal:  Invest Ophthalmol Vis Sci       Date:  2012-11-09       Impact factor: 4.799

8.  Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial.

Authors:  Robert K Koenekoop; Ruifang Sui; Juliana Sallum; L Ingeborgh van den Born; Radwan Ajlan; Ayesha Khan; Anneke I den Hollander; Frans P M Cremers; Janine D Mendola; Ava K Bittner; Gislin Dagnelie; Ronald A Schuchard; David A Saperstein
Journal:  Lancet       Date:  2014-07-13       Impact factor: 79.321

9.  Thickness of receptor and post-receptor retinal layers in patients with retinitis pigmentosa measured with frequency-domain optical coherence tomography.

Authors:  Donald C Hood; Christine E Lin; Margot A Lazow; Kirsten G Locke; Xian Zhang; David G Birch
Journal:  Invest Ophthalmol Vis Sci       Date:  2008-11-14       Impact factor: 4.799

Review 10.  Neural remodeling in retinal degeneration.

Authors:  Robert E Marc; Bryan W Jones; Carl B Watt; Enrica Strettoi
Journal:  Prog Retin Eye Res       Date:  2003-09       Impact factor: 21.198

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Review 1.  Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications.

Authors:  Isabel Pinilla; Victoria Maneu; Laura Campello; Laura Fernández-Sánchez; Natalia Martínez-Gil; Oksana Kutsyr; Xavier Sánchez-Sáez; Carla Sánchez-Castillo; Pedro Lax; Nicolás Cuenca
Journal:  Antioxidants (Basel)       Date:  2022-05-30

2.  Morphologic characteristics and clinical significance of the macular-sparing area in patients with retinitis pigmentosa as revealed by multicolor imaging.

Authors:  Guodong Liu; Qing Du; Khusbu Keyal; Fang Wang
Journal:  Exp Ther Med       Date:  2017-09-29       Impact factor: 2.447

3.  Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations.

Authors:  Mays Talib; Mary J van Schooneveld; Roos J G van Duuren; Caroline Van Cauwenbergh; Jacoline B Ten Brink; Elfride De Baere; Ralph J Florijn; Nicoline E Schalij-Delfos; Bart P Leroy; Arthur A Bergen; Camiel J F Boon
Journal:  Transl Vis Sci Technol       Date:  2019-08-19       Impact factor: 3.283

4.  Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT).

Authors:  Hendrik P N Scholl; Anthony T Moore; Robert K Koenekoop; Yuquan Wen; Gerald A Fishman; L Ingeborgh van den Born; Ava Bittner; Kristen Bowles; Emily C Fletcher; Frederick T Collison; Gislin Dagnelie; Simona Degli Eposti; Michel Michaelides; David A Saperstein; Ronald A Schuchard; Claire Barnes; Wadih Zein; Ditta Zobor; David G Birch; Janine D Mendola; Eberhart Zrenner
Journal:  PLoS One       Date:  2015-12-10       Impact factor: 3.240

Review 5.  Leber congenital amaurosis/early-onset severe retinal dystrophy: current management and clinical trials.

Authors:  Malena Daich Varela; Thales Antonio Cabral de Guimaraes; Michalis Georgiou; Michel Michaelides
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  5 in total

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