Postreceptor Neuronal Degeneration in Pseudoxanthoma Elasticum

Abstract

Purpose : To determine the association of age, presence of optic nerve head drusen (ONHD) and number of previous intravitreal anti-VEGF injections with inner retinal layer thicknesses in patients with pseudoxanthoma elasticum (PXE).

Methods : In this retrospective study, longitudinal spectral domain optical coherence tomography (OCT) imaging data form patients with PXE were compared to controls. A custom deep-learning-based segmentation algorithm was trained and validated to quantify the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and the inner nuclear layer (INL) for each ETDRS-subfield.The association of age, number of anti-VEGF injections and ONH drusen with the RNFL/GCL/IPL/INL thickness as dependent variable were investigated using mixed model regression. The model was applied for a macular ring including all outer ETDRS subfields with an ETDRS grid centered to the fovea.

Results : Fifty-three eyes of 30 patients with PXE were compared to 100 eyes of 100 controls. The mean age was (median [IQR]) 54.0 [46.3, 61.7] years for patients vs. 58.1 [36.6, 37.8] years for controls. In patients, ONHD were visible in 15 eyes from 13 patients and the number of anti-VEGF injections ranged from 0 to 55. In the multivariable analysis, age (-0.09 µm/year, p<0.001), the diagnosis of PXE (-1.80 µm, p=0.022) and an interaction term between age and the presence of ONHD (-0.22 µm/year, p=0.002) were significantly associated with the GCL thickness in the ring of all outer ETDRS subfields. Including the number of intravitreal injections did not improve the model fit. The RNFL was solely dependent on age without any influence of other parameters. The IPL showed significantly decreased thickness in patients (-4.79µm) compared to controls (P=0.015), but with a significant interaction of group and age (+0.11µm/year, P = 0.003) compatible with gliotic remodeling in older patients with concurrent atrophic changes.

Conclusions : This study demonstrates a significant association of ageing and ONHD with GCL thinning in patients with PXE. Given the severity of postreceptor neuronal degeneration in a subset of patients, neuroprotective therapy once available would warrant consideration. Further, emerging anti-VEGF agents, which allow for less frequent intravitreal injections and/or smaller injections volumes, may be considered to minimize transient intraocular pressure elevations with potential adverse effects on the GCL.

This is a 2021 ARVO Annual Meeting abstract.