Measurement Reliability and Functional Validity of Bruch's Membrane Calcification in Pseudoxanthoma Elasticum: PROPXE Study Report 2.
Giger Jason A W, Ansari Georg, Terry Sharon F, Charbel Issa Peter, Pfau Kristina, Pfau Maximilian
AI Summary
This study found reliable measurement of Bruch's membrane calcification in PXE, which increases with age and strongly correlates with delayed rod-mediated dark adaptation, making it a potential early severity marker for treatment.
Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusions
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.
MeSH Terms
Shields Classification
Key Concepts5
The temporal inner peau d'orange boundary extent in patients with Pseudoxanthoma elasticum (PXE) varied significantly with age (+4.35 deg/decade, P = 0.001) in a prospective natural history study (PROPXE, NCT05662085) including 26 patients (14 women and 12 men; median age = 55 years, interquartile range = 43-59 years).
A greater temporal inner peau d'orange boundary extent in patients with Pseudoxanthoma elasticum (PXE) 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 in a prospective natural history study (PROPXE, NCT05662085) including 26 patients.
Delayed dark adaptation at 8 degrees and 15 degrees eccentricity (from the fovea) manifested in patients with Pseudoxanthoma elasticum (PXE) once the temporal inner peau d'orange boundary exceeded 27.15 degrees and 32.56 degrees eccentricity (from the optic nerve head), respectively, in a prospective natural history study (PROPXE, NCT05662085) including 26 patients.
Patients with Pseudoxanthoma elasticum (PXE) demonstrate significant rod-mediated dark adaptation deficits correlating with the temporal inner peau d'orange boundary extent, supporting the use of Bruch's membrane calcification extent as an objective marker for disease severity and facilitating earlier therapeutic intervention in PXE.
The temporal inner peau d'orange boundary in patients with Pseudoxanthoma elasticum (PXE) showed excellent inter-reader (intraclass correlation coefficient [ICC] = 0.92) and inter-visit reliability (ICC = 0.95) in a prospective natural history study (PROPXE, NCT05662085) including 26 patients (14 women and 12 men; median age = 55 years, interquartile range = 43-59 years).
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