Insights Into PROM1-Macular Disease Using Multimodal Imaging

Area of Science:

• Ophthalmology
• Genetics
• Medical Imaging

Background:

• PROM1-macular dystrophy, also known as Stargardt disease 4, is a rare inherited retinal disorder.
• Understanding its distinct features is crucial for accurate diagnosis and potential therapeutic development.

Purpose of the Study:

• To characterize the multimodal imaging features of genetically confirmed PROM1-macular dystrophy.
• To differentiate PROM1-macular dystrophy from other macular dystrophies, particularly recessive Stargardt disease.

Main Methods:

• Prospective study of 18 patients (36 eyes) with genetically confirmed PROM1 mutations.
• Multimodal imaging including short-wavelength autofluorescence (SW-AF), quantitative fundus autofluorescence (qAF), near-infrared autofluorescence (NIR-AF), and spectral-domain optical coherence tomography (SD-OCT).
• Genetic confirmation via exome sequencing.

Main Results:

• All patients exhibited varying degrees of maculopathy.
• Granular deposits were observed in SW-AF and NIR-AF, correlating with ellipsoid zone loss on SD-OCT.
• qAF and mean NIR-AF levels were generally within normal limits, unlike in recessive Stargardt disease.

Conclusions:

• PROM1-macular dystrophy presents unique imaging findings that may overlap with, but are distinct from, recessive Stargardt disease.
• Elevated bisretinoid lipofuscin accumulation may not be a key feature in PROM1 disease pathophysiology.
• Quantitative autofluorescence imaging shows promise for early differential diagnosis and identifying therapeutic targets.