Quantification of Bruch’s Membrane calcification in Pseudoxanthoma Elasticum: a proof‐of‐concept study using SD‐OCT

Purpose Progressive calcification of Bruch’s membrane (BM) causes considerable visual morbidity in patients with pseudoxanthoma elasticum (PXE). Since calcification is hyperreflective in SD‐OCT imaging, our aim was to quantify BM calcification using SD‐OCT. Methods We performed a ‘proof of concept’ study with 45 PXE patients under 40 years and 25 age‐matched controls. Spectralis HRA‐OCT imaging was performed, consisting of 7 macular B‐scans with 250 µm distance in between. Retinal segmentation was performed using OCT Explorer (and visually verified per B‐scan on correct segmentation and an intact outer retinal layer). Matlab was used to extract and average z‐axis intensity profiles for each set of B‐scans. Mean layer intensities normalized to the GCL‐IPL layer were used for descriptive analysis. Intensity ratios, defined as the retinal pigment epithelium (RPE)‐BM peak intensity relative to another layer, were calculated to quantify RPE‐BM intensity. These ratios were compared with the control group to find a discriminative value using ROC analysis. Results The age of the groups were comparable, with a mean age of 27.0 years in PXE patients and 26.9 years in the control group. The median normalized intensity of the RPE‐BM was 34.0 (IQR 24.7–42.3) in patients with PXE, compared to 20.4 (IQR 17.2–24.4) in normal controls (p < 0.001). The RPE‐BM/ ellipsoid zone (EZ) ratio was the most discriminative with an AUC of 0.97 (95% CI 0.92–1). In PXE patients, the median ratio was 1.79 (IQR 1.33; 2.63) compared to 0.75 in controls (IQR 0.61; 0.97). The RPE‐BM/EZ ratio increased with age in PXE patients: 1.14 (IQR 1.01–1.32) in patients under 20 (n = 7), 1.81 (IQR 1.35–2.19) in patients aged 20–30 years (n = 22) and 2.35 (IQR 1.68–3.08) in patients aged 30–40 (n = 16) (p = 0.010). Conclusions We demonstrated that BM calcification is quantifiable as hyperreflectivity in young PXE patients, that the RPE‐BM/EZ intensity ratio can discriminate between PXE and normal controls, and that this intensity ratio increases with age.