Improving early detection of progressive retinal neurodegeneration
File(s)
Author(s)
Yap, Timothy
Type
Thesis
Abstract
Background: Progressive retinal neuronal cell loss underlies several sight-threatening conditions. Monitoring this process is critical in preventing sight loss. There is a clinical unmet need demanding we achieve objective quantification to improve early detection and prediction of disease progression, empowering practitioners to make effective clinical decisions.
Methods: Firstly, the analysis of existing technology output was optimised, with the tools acquired then used to assess novel methods. Chapters two and three present novel analysis and presentation of circumpapillary and posterior pole optical coherence tomography (OCT) imaging. Experimental biomarkers for progression including the Water Drinking Test (WDT) (chapter four), and Detection of Apoptosing Retinal Cells (DARC) in-vivo imaging in a spectrum of retinal neurodegenerative diseases (chapters five and six) and experimental islet cell transplantation are presented thereafter.
Results: The use of angular histograms and dynamic clustering in Rose Plot Analysis was shown to improve inter-observer agreement and early detection when diagnosing glaucomatous progression in OCT scans. Pointwise analysis of posterior pole data also was shown to detect progressing eyes. The WDT demonstrated comparable results to the current clinical standard for diurnal IOP monitoring with important time and cost saving implications; however, it did not show correlation with progressive retinal neurodegeneration. DARC successfully visualised human retinal cells in healthy subjects, glaucoma, optic neuritis, age-related macular degeneration, and Down’s syndrome, with successful differentiation between progressing and non-progressing glaucomatous eyes. The use of DARC imaging was shown to successfully highlight retinal cells in a diabetic mouse model, although it did not correlate with disease status. The technique of islet cell anterior chamber transplantation was achieved and refined.
Conclusion: This work has improved our ability to detect progressive retinal neurodegeneration using both existing and novel technologies, whilst expanding our knowledge and experience in using certain experimental techniques in the study of such diseases.
Methods: Firstly, the analysis of existing technology output was optimised, with the tools acquired then used to assess novel methods. Chapters two and three present novel analysis and presentation of circumpapillary and posterior pole optical coherence tomography (OCT) imaging. Experimental biomarkers for progression including the Water Drinking Test (WDT) (chapter four), and Detection of Apoptosing Retinal Cells (DARC) in-vivo imaging in a spectrum of retinal neurodegenerative diseases (chapters five and six) and experimental islet cell transplantation are presented thereafter.
Results: The use of angular histograms and dynamic clustering in Rose Plot Analysis was shown to improve inter-observer agreement and early detection when diagnosing glaucomatous progression in OCT scans. Pointwise analysis of posterior pole data also was shown to detect progressing eyes. The WDT demonstrated comparable results to the current clinical standard for diurnal IOP monitoring with important time and cost saving implications; however, it did not show correlation with progressive retinal neurodegeneration. DARC successfully visualised human retinal cells in healthy subjects, glaucoma, optic neuritis, age-related macular degeneration, and Down’s syndrome, with successful differentiation between progressing and non-progressing glaucomatous eyes. The use of DARC imaging was shown to successfully highlight retinal cells in a diabetic mouse model, although it did not correlate with disease status. The technique of islet cell anterior chamber transplantation was achieved and refined.
Conclusion: This work has improved our ability to detect progressive retinal neurodegeneration using both existing and novel technologies, whilst expanding our knowledge and experience in using certain experimental techniques in the study of such diseases.
Version
Open Access
Date Issued
2023-01-14
Date Awarded
01/09/2023
License URL
Advisor
Cordeiro, M. Francesca
Bloom, Philip
Normando, Eduardo
Sponsor
St Mary's Development Trust (Charity)
Grant Number
WSSS_P72007
Publisher Department
Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)