Optical Coherence Tomography Abnormalities in NOTCH3 Mutation Carriers: A Matched Case-Control Study From UK Biobank

Area of Science:

• Ophthalmology
• Genetics
• Neurology

Background:

• NOTCH3 mutations are associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
• Early detection of neurological changes is crucial for managing NOTCH3-related disorders.

Purpose of the Study:

• To identify retinal biomarkers in NOTCH3 mutation carriers using optical coherence tomography (OCT).
• To investigate the association between NOTCH3 mutations and retinal structural changes.

Main Methods:

• A matched case-control study using UK Biobank data (2006-2010).
• Inclusion of 134 participants (67 cases, 67 controls) with macular OCT scans and cognitive assessments.
• Comparison of macular thickness and retinal nerve fiber layer (RNFL) between NOTCH3 mutation carriers and controls.

Main Results:

• NOTCH3 carriers showed thinner macular inner subfield and RNFL compared to controls.
• No significant differences in visual acuity were observed.
• Cognitive performance was worse in NOTCH3 carriers for prospective memory, verbal, numerical reasoning, and processing speed.

Conclusions:

• Reduced macular inner subfield and RNFL thickness are associated with NOTCH3 mutations.
• These retinal changes may indicate early pericyte dysfunction and microvascular ischemia.
• Longitudinal studies are recommended to explore the relationship with disease progression.