| Summary: | RPGR-associated retinitis pigmentosa is among the most severe forms of RP and is an important target for gene therapy trials. There is however a lack of robust clinical data on this condition. The aim of this thesis is therefore to investigate and characterise the natural history with protocol-driven, prospectively acquired structural and functional data on molecularly confirmed subjects. Investigations into retinal structure were conducted with data obtained from protocol driven spectral domain-optical coherence tomography and autofluorescence imaging. Visual function assessments were performed with visual acuity, contrast senstivity and Octopus 900 static perimetry testing using a customised grid. Three-dimensional topographic models were created from perimetry data with the use of advanced software to produce volumetric metrics for further interrogation. Quantitative analyses of structure or function were comprehensively undertaken with each modality to bilaterally characterise baseline dimension and progression rates of subjects. In addition, a broad range of metrics were investigated to identify ones that are most sensitive and suitable for use in characterising the natural history, with the expectation that these metrics will be utilised in studying future outcomes of treatment trials. In general, good overall interocular symmetry was found however significant variation exists across subjects. Indices to quantify intraocular symmetry were constructed and explored. Associations between progression, age, baseline dimension and genotype were investigated. Younger subjects typically possessed greater baseline dimensions. Faster rates of progression were found in those with better baseline structure and function. Exponential decline rates for each modality were calculated with a mixed-models method using pooled data from the cohort to estimate overall progression. In comparison to functional metrics, structural metrics were more sensitive in detecting change with the characterisation of greater progression rates. The optical coherence tomography based ellipsoid zone (EZ) width metric was found to be more precise compared to the EZ area metric. With regards to autofluorescence based metrics, those derived from outer borders of hyperautofluorescent rings were superior to metrics derived from inner borders of rings. Ring area was found to be more robust compared to ring diameter metric. Functional metrics are nevertheless important as they reflect the subject's visual experience. Visual function in the earlier stages of disease is best characterised by metrics of peripheral function with decline in the later stages better characterised by metrics of central function. Work presented in this thesis is expected to provide a much-needed resource to inform recently commenced treatment trials, in addition to providing prognostic information to clinicians caring for individuals with the condition.
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