Spectral Domain Optical Coherence Tomography in Retinal Vasculopathy With Cerebral Leukoencephalopathy and Systemic Manifestations: A Monogenic Small Vessel Disease.

Background: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including retina and brain, are affected. Analyzing retinal anatomy is increasingly used as a biomarker for ophthalmological and neurological disorders (due to the shared embryological origin of retina and brain). Optical coherence tomography (OCT) provides a noninvasive cross-sectional visualization of optic disc and macula. We aimed to use OCT to investigate retinal layer thickness in RVCL-S.

Methods: Cross-sectional, 17 TREX1 mutation carriers (34 eyes) and 9 controls (18 eyes) underwent comprehensive ophthalmologic assessment followed by spectral domain OCT for measuring peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). Secondary outcomes included measuring thickness of individual macular retinal layers and peripapillary sectors. Findings were analyzed using generalized estimating equations to account for intereye correlation.

Results: TREX1 mutation carriers had decreased pRNFL thickness (median [interquartile range] 76 [60-99] vs 99 [87-108] µm, P < 0.001) and TMV (8.1 [7.4-8.5] vs 8.7 [8.4-8.8] mm3, P = 0.006) compared with controls. With the exception of the temporal sector, the thickness of all peripapillary sectors was decreased in TREX1 mutation carriers. Ganglion cell layer (30 [22-37] vs 39 [36-41] µm, P < 0.001) and inner plexiform layer (27 [24-34] vs 34 [31-35], P = 0.001) were thinner in TREX1 mutation carriers. Notably, in 9 of 12 eyes with normal funduscopic examination, retinal thinning was already detected.

Conclusions: RVCL-S, which may serve as a vascular retinopathy model, is associated with retinal thinning in the peripapillary and macular area. OCT findings can potentially serve as early biomarkers for RVCL-S and other vascular retinopathies.