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

The purpose of this study was to assess the inter-reader and inter-visit reliability of en face Bruch's membrane (BrM) calcification measurements in Pseudoxanthoma elasticum (PXE), investigate how the patient's age influences the BrM calcification extent, and evaluate the association between BrM calcification and delayed rod-mediated dark adaptation.

This prospective natural history study (PROPXE, ClinicalTrials.gov ID: NCT05662085) included 26 patients (14 women and 12 men; median age = 55 years, interquartile range = 43-59 years) diagnosed with PXE. Participants underwent comprehensive ophthalmic evaluations, including widefield infrared reflectance imaging (up to 83 degrees eccentricity) and dark adaptometry at retinal eccentricities of 8 degrees, 15 degrees, 30 degrees, and 46 degrees along the temporal retina. The primary outcomes were inter-visit and inter-reader reliability of the temporal inner peau d'orange boundary extent, its correlation with age, and its relationship with rod-intercept time (RIT) during dark adaptation.

The temporal inner peau d'orange boundary showed excellent inter-reader and inter-visit reliability (inter-reader intraclass correlation coefficient [ICC] = 0.92 and inter-visit ICC = 0.95) and varied significantly with age (+4.35 deg/decade, P = 0.001). A greater temporal inner peau d'orange boundary extent was strongly associated with delayed rod-mediated dark adaptation at 8 degrees (+1.05 min/deg, P = 0.002) and 15 degrees (+0.91 min/deg, P = 0.001) eccentricities. A threshold effect was observed, with delayed dark adaptation at 8 degrees and 15 degrees eccentricity (from the fovea; i.e. 23 degrees and 30 degrees from the optic nerve head) manifesting once the temporal inner boundary exceeded 27.15 degrees and 32.56 degrees eccentricity (from the optic nerve head), respectively.

Patients with PXE demonstrate significant rod-mediated dark adaptation deficits correlating with the temporal inner peau d'orange boundary extent. These findings support the use of BrM calcification extent as an objective marker for disease severity, facilitating earlier therapeutic intervention than currently possible in PXE.