Measurement Reliability and Functional Validity of Bruch's Membrane Calcification in Pseudoxanthoma Elasticum: PROPXE...

Area of Science:

• Ophthalmology
• Medical Imaging
• Retinal Diseases

Background:

• Pseudoxanthoma elasticum (PXE) is a rare genetic disorder affecting elastic tissues, including Bruch's membrane (BrM) in the eye.
• BrM calcification is a hallmark of PXE, but its measurement reliability and clinical significance require further investigation.
• Assessing BrM calcification may offer insights into disease progression and visual function deficits in PXE patients.

Purpose of the Study:

• To evaluate the inter-reader and inter-visit reliability of en face BrM calcification measurements in PXE.
• To determine the influence of patient age on the extent of BrM calcification.
• To examine the association between BrM calcification and impaired rod-mediated dark adaptation in PXE.

Main Methods:

• A prospective natural history study (PROPXE) involving 26 PXE patients.
• Ophthalmic evaluations included widefield infrared reflectance imaging and dark adaptometry at various retinal eccentricities.
• Primary outcomes focused on reliability of temporal inner peau d'orange boundary extent, its correlation with age, and relationship with rod-intercept time (RIT).

Main Results:

• Excellent inter-reader (ICC=0.92) and inter-visit (ICC=0.95) reliability for temporal inner peau d'orange boundary measurements.
• BrM calcification extent significantly increased with age (4.35 deg/decade, P=0.001).
• Greater BrM calcification was strongly associated with delayed dark adaptation at 8 and 15 degrees eccentricity (P=0.002 and P=0.001, respectively).

Conclusions:

• PXE patients exhibit significant deficits in rod-mediated dark adaptation linked to BrM calcification extent.
• BrM calcification measurements serve as an objective biomarker for PXE disease severity.
• These findings may enable earlier therapeutic interventions in PXE.