The Natural History of Bruch's Membrane Calcification in Pseudoxanthoma Elasticum

Purpose: To describe the natural history of Bruch's membrane (BM) calcification in patients with pseudoxanthoma elasticum (PXE). Design: Retrospective cohort study. Participants: Both eyes of 120 PXE patients younger than 50 years, 78 of whom had follow-up imaging after more than 1 year. Methods: All patients underwent multimodal imaging, including color fundus photography, near-infrared reflectance (NIR) imaging, and late phase indocyanine green angiography (ICGA). We determined the distance from the optic disc to the central and temporal border of peau d'orange on NIR, expressed in horizontal optic disc diameter (ODD). The length of the longest angioid streak was classified into 5 zones. Main Outcome Measures: Age-specific changes of peau d'orange, angioid streaks, and ICGA hypofluorescence as surrogate markers for the extent of BM calcification. Results: In cross-sectional analysis, longer angioid streaks were associated with increasing age (P < 0.001 for trend). The temporal border of peau d'orange showed a weak association with increasing age (β = 0.02; 95% confidence interval [CI], 0.00–0.04), whereas the central border showed a strong association (β = 0.12; 95% CI, 0.09–0.15). Longitudinal analysis revealed a median shift of the central border to the periphery of 0.08 ODD per year (interquartile range [IQR], 0.00–0.17; P < 0.001). This shift was more pronounced in patients younger than 20 years (0.12 ODD per year [IQR, 0.08–0.28]) than in patients older than 40 years (0.07 ODD per year [IQR, –0.05 to 0.15]). The temporal border did not shift during follow-up (P = 0.69). New or growing angioid streaks were detected in 39 of 156 eyes (25%). The hypofluorescent area on ICGA was visible only in the fourth or fifth decade and correlated with longer angioid streaks. Conclusions: In PXE patients, the speckled BM calcification slowly confluences during life. The location of the temporal border of peau d'orange remains rather constant, whereas the central border shifts to the periphery. This suggests the presence of a predetermined area for BM calcification. A larger ICGA hypofluorescent area correlates with older age and longer angioid streaks, which implies that it depends on the degree of BM calcification.