Optimising the clinical utility of the photopic negative response to probe changes in glaucoma
AffiliationOphthalmology (Eye & Ear Hospital)
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2021-08-07.
© 2019 Dr. Jessica Tang
Glaucoma is one of the leading causes of irreversible blindness and early detection and treatment are key to preventing or slowing the progression of vision loss. An objective, non-invasive method to detect early functional changes in glaucoma would be invaluable, and a potential surrogate marker of retinal ganglion cell health may lie in the photopic negative response (PhNR) of the electroretinogram (ERG). Purpose: To develop and validate a reliable testing protocol for the PhNR recorded using a portable ERG device (RETeval®) that can be easily implemented in clinical practice. Methods: Normal controls and glaucoma participants were recruited for the study. Responses were elicited using a red stimulus on a steady blue background with the RETeval®. A comparison of baseline detrending methods as well as electrode performance was evaluated between the groups. The PhNR stimulus-response function was characterised, and the correlation between PhNR parameters and current measures of retinal structure and function were assessed. The sensitivity of the PhNR to detect glaucomatous changes was evaluated in glaucoma participants receiving treatment for intraocular pressure lowering. The PhNR was also used to follow glaucoma participants over 12-months to assess its relative ability to detect disease progression. Results: A method of baseline detrending was developed which improved the test-retest repeatability of the PhNR without compromising its clinical utility in glaucoma. Sensor strip electrodes provided a viable alternative to conventional Dawson, Trick and Litzkow (DTL) electrodes, although had inferior signal-to-noise performance that may reduce the sensitivity to detect subtle changes in disease. Measuring the PhNR across a range of stimuli to determine the maximum response provided reliable data and may be more appropriate than a single stimulus strength. However, the maximum response showed only weak correlation with standard automated perimetry and retinal nerve fibre layer thickness in glaucoma. With the optimised protocol, short-term changes in the PhNR were detected after intraocular pressure lowering in a subset of participants. Disease progression was also suggested by monitoring the PhNR over 12-months in a pilot study. Conclusion: This body of work developed a standardised, reliable method for PhNR recording with a portable ERG device which can complement current tests in monitoring glaucoma progression and evaluating treatment response in the clinic.
Keywordsglaucoma; photopic negative response; electroretinogram
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