Functional imaging of the outer retina using high fidelity imaging retinal densitometry: exploring the relationship between visual pigment kinetics and AMD pathology

Pattni, Krishna 2024. Functional imaging of the outer retina using high fidelity imaging retinal densitometry: exploring the relationship between visual pigment kinetics and AMD pathology. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Imaging retinal densitometry (IRD) is a technique with the unique ability to measure rod and cone visual pigment kinetics in vivo and reliably map them topographically. This project describes the first application of the technology to investigate age-related macular degeneration (AMD), a progressive disease affecting the central retina and a leading cause of sight impairment in the UK. Impairment of dark adaptation, a psychophysical process underpinned by visual pigment synthesis, is a well-established functional biomarker of early- stage AMD, typically preceding impactful vision loss. IRD offered a novel opportunity to investigate the relationship between visual pigment synthesis and retinal pathology in early to intermediate AMD. These structural changes, extensively documented through multimodal imaging including OCT, are critical clinical markers of disease progression. Initially, IRD was combined with OCT to assess visual pigment optical density and photoreceptor outer segment length in 19 healthy participants. This data allowed a model to be proposed describing the relationship between these parameters, accounting for retinal eccentricity and the physiological differences between rod and cone photoreceptors. Of significance, rod visual pigment concentration was found to be only 47% that of cones, we propose this could be due to the near constant exposure of humans to light, resulting in a reduced rhodopsin content. For the AMD-related research questions, 106 participants were screened, with 32 individuals with early to intermediate AMD and 32 age-matched healthy controls meeting the criteria. IRD was used to assess visual pigment optical density and recovery rates in rod and cone photoreceptors, offering a ‘functional’ measure. Conventional retinal imaging, including colour fundus photography, near-infrared imaging, and OCT, provided ‘structural’ measures. This data enabled a comparative analysis of the structure-function relationship between visual pigment synthesis and the presence of soft drusen, reticular pseudodrusen (RPD), and ellipsoid zone (EZ) disruption. The relationship between soft drusen parameters, such as height and area, with visual pigment recovery rate was also established using multilevel modelling. Key findings revealed no significant difference in rod optical density between control and AMD groups (0.076 OD vs. 0.075 OD). However, cone optical density was reduced in AMD (0.143 OD) compared to controls (0.180 OD). Visual pigment recovery rates were slower in AMD (0.002 OD/min for rods, 0.024 OD/min for cones) compared to controls (0.004 OD/min for rods, 0.042 OD/min for cones). Cone, but not rod, recovery rate, was significantly impacted at all retinal locations in the presence of ellipsoid zone impairment/disruption. Drusen height, but not area, significantly reduced visual pigment recovery in AMD retinas. The presence of soft drusen may impact visual pigment synthesis rates beyond the retinal areas at which it is present. Conversely, presence of RPD significantly reduced both rod and cone recovery rates when comparing areas within the same retina, likely due to its location between the RPE and photoreceptors, directly impeding mechanisms relating to visual pigment synthesis. IRD parameters provide valuable insight into the impact of AMD-related lesions on outer retinal function and offer the potential as an effective test of outer retinal health. This functional assessment could be powerful addition in future clinical trials targeting early to intermediate AMD.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Optometry and Vision Sciences
Funders:	College of Optometrists
Date of First Compliant Deposit:	12 February 2025
Last Modified:	12 Feb 2025 12:30
URI:	https://orca.cardiff.ac.uk/id/eprint/176094

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