Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schliessleder, G.
STRUCTURE AND FUNCTION ANALYSIS IN PROM1-RELATED RETINOPATHY
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2024. pp. 105
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Riedl Regina
- Strauß Rupert
- Wedrich Andreas
- Altmetrics:
- Abstract:
- Background: There is a limited understanding of how PROM1 sequence variants specifically impact cone photoreceptors. This thesis aimed to investigate the structure and function of the retina, with a particular focus on cone photoreceptors, in patients with PROM1-associated retinal degeneration (PROM1-RD). Methods: Twelve patients from four pedigrees with potentially disease-causing variants in the PROM1 gene from the Moorfields Eye Hospital database were identified. Six study eyes were included in this institutional longitudinal cohort, which featured two assessments: the initial baseline examination and a follow-up after a 24-month interval. Visual acuity using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, areas of decreased autofluorescence via fundus autofluorescence (FAF), total retinal thickness, and individual layer thickness by spectral domain optical coherence tomography (SD-OCT), and cone density (the primary endpoint) using adaptive optics scanning light ophthalmoscopy (AOSLO), were measured. SD-OCT outcome measures were compared to normative data provided by the Moorfields Eye Hospital (MEH). Results: AOSLO imaging of assessable quality was successful for the right eyes of four patients. Imaging of a comparable standard could be successfully repeated for two eyes after two years. Challenges encountered included unstable fixation and extensive atrophy. At baseline, the best-corrected visual acuity (BCVA) ranged from 35 to 85 ETDRS letters. All four eyes showed altered autofluorescence patterns. The outer segment layer thickness was significantly reduced in comparison to the normative data. Cone density was quantified in the central area and/or at varying distances from the fovea. In the two eyes with follow-up examinations after two years, reductions in the thickness of outer retinal layers and cell density exceeding the standard deviation, as well as a decrease in BCVA, were observed. In one eye, the area of decreased autofluorescence, as determined by FAF, expanded, while in the other, the autofluorescence pattern remained unchanged. Conclusion: This study is the first to investigate PROM1-associated retinal degeneration at the cellular level, including AOSLO imaging. It encompasses cases of both autosomal dominant (AD) and autosomal recessive (AR) inheritance and provides longitudinal data. AOSLO imaging enabled the measurement of cone density despite significant thinning of the outer segments, as seen in SD-OCT analysis. The evidence of residual cones, even in advanced stages of PROM1-RD, may represent a promising opportunity for potentially cone-directed therapeutic interventions.