Doctoral defence: Maarjaliis Paavo “Short-wavelength and near-infrared autofluorescence imaging in recessive stargardt disease, choroideremia, PROM1-macular dystrophy and ocular albinism”

On 19 June at 14:00 Maarjaliis Paavo will defend her doctoral thesis “Short-wavelength and near-infrared autofluorescence imaging in recessive stargardt disease, choroideremia, PROM1-macular dystrophy and ocular albinism” for obtaining the degree of Doctor of Philosophy (in Medicine).

Supervisor:
Associate Professor Kuldar Kaljurand, University of Tartu
Janet R. Sparrow, Columbia University (USA)

Opponent: 
Professor Carel Hoyng, Radboud UMC (the Netherlands)

Summary
Inherited retinal diseases are the leading cause of visual impairment among the working age-group in the developed countries. Because of genetic and phenotypical heterogeneity, diagnosis and understanding pathogenesis of inherited retinal disease has been challenging. Retinal imaging studies which are noninvasive, are an invaluable source of information. Fundus autofluorescence (FAF) utilizes natural fluorophores to create an image of the retina. Lipofuscin is the primary source for short-wavelength autofluorescence (SW-AF) and melanin for near-infrared autofluorescence (NIR-AF). The amount and distribution of these fluorophores changes in the different disease processes and is detectable in FAF images. 

In this study we analyzed SW-AF and NIR-AF images in cases of genetically confirmed recessive Stargardt disease (STGD1), choroideremia, PROM1-macular disease and ocular albinism. The aim was to better understand the sources of FAF in conditions with varying levels of lipofuscin or melanin as well as to quantify FAF signal intensities.  We also aimed at finding new clinical implications for autofluorescence imaging in evaluating inherited retinal disease. 

We confirmed that melanin is the major source of NIR-AF signal by analyzing ocular albinism carriers and mice models with varying fundus pigmentation, but that it can also modulate SW-AF signal strength. We also found that lipofuscin likely contributes to NIR-AF signal intensity in cases with excessive bisretinoid lipofuscin levels like seen in STGD1. The analysis of choroideremia and STGD1 patients showed that retinal pigment epithelium atrophy causes loss of signal in both SW-AF and NIR-AF, but NIR-AF could be more sensitive in detecting early cell degeneration. Quantifying the autofluorescence signal intensity helps to further understand disease processes as it is an indirect measure for levels of retinal fluorophores. We showed PROM1-macular dystrophy does not show elevated levels of SW-AF indicating that excessive lipofuscin accumulation is likely not part of its disease mechanism.  That knowledge is valuable in differentiating it from phenotypically similar STGD1 or when developing therapeutic approaches. SW-AF and NIR-AF signal are both valuable biomarkers for evaluating retinal health without any invasive procedures.