Retinal Features and Preserved Vision in ENPP1 Deficiency: Long-Term Insights from Multimodal Imaging and...

Loss-of-function variants in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) impair pyrophosphate homeostasis, leading to pathological ectopic calcification. We present the first long-time longitudinal single-case ophthalmic assessment of a male patient with ENPP1 deficiency. Multimodal evaluations included spectral-domain optical coherence tomography (OCT), OCT angiography (OCT-A), infrared scanning laser ophthalmoscopy (IR-SLO), fundus autofluorescence, fluorescein angiography, dark adaptometry, full-field and multifocal electroretinography (ERG), and the measurement of visual evoked potentials (VEP). All data were compared to normative data obtained from age-matched controls in our clinic. Visual acuity declined slightly from 1.0 to 0.7 (OD) and 0.63 (OS) within ten years. IR-SLO revealed numerous retinal speckles without structural OCT correlates or progression. OCT showed subtle changes in layer-specific retinal thickness, without reaching significance compared to healthy controls. OCT-A revealed reduced flow densities in superficial and deep capillary plexuses and preserved foveal avascular zone metrics. Scotopic ERG and multifocal ERG amplitudes were reduced and some ERG implicit times increased. Adaptometry showed a reduced rod sensitivity. Despite systemic ectopic calcification, retinal structure and function remained largely preserved. The findings suggest mild subclinical retinal involvement and support the use of electrophysiology as candidate noninvasive biomarkers for monitoring. Distinct from ABCC6-related PXE, ENPP1 deficiency may exhibit a slower, more stable retinal course.