Date of Award
1-1-2019
Document Type
Open Access Thesis
Degree Name
Medical Doctor (MD)
Department
Medicine
First Advisor
Ron A. Adelman
Second Advisor
Stephen H. Tsang
Abstract
Retinitis pigmentosa (RP) is a group of genetically and clinically heterogeneous inherited retinal degenerative diseases with no known cure to date. The recent gene therapy treatment for Leber’s congenital amaurosis and RP caused by mutations in RPE65 have resulted in dramatic improvements in vision, leading to excitement for other potential gene therapies on the horizon. Upcoming clinical trials will be targeting patients with specific mutations, and measurements of disease progression will be needed for each genetic subtype of RP in order to determine whether treatments are successful. In this retrospective cohort study, we examined 27 RP patients with confirmed autosomal dominant mutations in the rhodopsin gene by monitoring rates of progression as measured structurally with ellipsoid zone (EZ) line width on spectral domain optical coherence tomography (SD-OCT), horizontal and vertical hyperautofluorescent ring diameters on short wavelength fundus autofluorescence (SW-FAF), and as measured functionally with 30 Hz flicker amplitudes on electroretinography (ERG). Each structural parameter was measured twice by the author four weeks apart. The mean rates of progression were -158.5 μm per year (-8.4%) for EZ line widths, -122.7 μm per year (-3.5%) for horizontal diameters, and -108.3 μm per year ( 3.9%) for vertical diameters. High test-retest reliability was observed for the parameters (EZ line intraclass coefficient [ICC] = 0.9989, horizontal diameter ICC = 0.9889, vertical diameter ICC = 0.9771). The three parameters were also correlated with each other (r = 0.9325 for EZ line and horizontal diameter; r = 0.9081 for EZ line and vertical diameter; r = 0.9630 for horizontal and vertical diameters). No significant changes in ERG amplitude were seen. The subjects were classified by rhodopsin mutation class (I, IIa, IIb, III) and morphology of the hyperautofluorescent ring (typical vs. atypical). No significant differences in rates of structural progression were observed by rhodopsin mutation class or by ring morphology. Finally, higher rates of asymmetry of progression between the left and right eyes were detected for EZ line width (23% of subjects), horizontal diameter (17%), and vertical diameter (25%), as compared to studies on other forms of RP.
Recommended Citation
Chan, Lawrence, "Multimodal Imaging And Asymmetry Of Disease Progression In Rhodopsin-Associated Autosomal Dominant Retinitis Pigmentosa" (2019). Yale Medicine Thesis Digital Library. 3480.
https://elischolar.library.yale.edu/ymtdl/3480
