Neurodegeneration in systemic lupus erythematosus: layer by layer retinal study using optical coherence tomography

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic, autoimmune and multisystemic disease. Recent studies with functional and structural magnetic resonance imaging and cognitive tests report an unexpectedly high frequency of central nervous system involvement, even in patients with asymptomatic SLE. The purpose of this study was to identify early signs of retinal neurodegeneration by comparing the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and all macular layers between patients with SLE without ophthalmologic manifestations and healthy controls. The effect of disease duration and systemic comorbidities was also studied. Methods Cross-sectional study, in which all participants underwent a complete ophthalmologic evaluation including retinal segmentation analysis with spectral domain-optical coherence tomography. Patients with SLE also received a detailed autoimmune disease specialist evaluation to assess the disease activity state and systemic involvement. For pRNFL thickness, the global and six peripapillary sectors were determined. Each macular layer thickness was determined in the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. A multiple linear regression analysis was performed to control for the effect of potential demographic, ophthalmic and systemic confounders. A second multivariable analysis, including patients with SLE only, was performed to assess the effect of disease-specific variables on the outcome measures. Results Sixty-eight eyes of 68 patients with SLE and 50 eyes of 50 healthy controls were considered. The pRNFL was significantly thinner in the SLE group globally (p = 0.026) and in the temporal superior (p = 0.007) and temporal (p = 0.037) sectors. In patients with SLE, chronic medication for hypercholesterolemia, hypertension and anticoagulants were associated with a significant thinning of the pRNFL. Patients with SLE presented significant thinning in the photoreceptor layer in five ETDRS areas (p < 0.05). Shorter disease duration was associated with greater photoreceptor thinning in all ETDRS subfields. Neuropsychiatric SLE, higher disease activity and cardiovascular risk factors were associated with a thinner photoreceptor layer. No differences were observed in overall retinal thickness or the remaining macular layers. Conclusion Patients with SLE present early signs of retinal neurodegeneration, as evidenced by a reduction in the photoreceptor layer and pRNFL. These signs are more pronounced in patients with higher cardiovascular risk burden or neuropsychiatric involvement.

Structural Features of Patients with Drusen-like Deposits and Systemic Lupus Erythematosus

“…Consistent with the results from Dias-Santos et al [ 17 ], we observed that the photoreceptor cell layer was significantly thinner in SLE patients with DLD compared to patients without DLD. As a tissue with high metabolic needs, the function of the cones and rods is directly dependent on the neighboring nourishing choriocapillaris [ 6 , 17 , 18 ].…”

“…Consistent with the results from Dias-Santos et al [ 17 ], we observed that the photoreceptor cell layer was significantly thinner in SLE patients with DLD compared to patients without DLD. As a tissue with high metabolic needs, the function of the cones and rods is directly dependent on the neighboring nourishing choriocapillaris [ 6 , 17 , 18 ]. As described above, SLE can involve the choroidal structures and blood flow and thus, leading to ischemia and atrophy in the retinal segments they supply with oxygen and nutrients [ 17 ].…”

“…As a tissue with high metabolic needs, the function of the cones and rods is directly dependent on the neighboring nourishing choriocapillaris [ 6 , 17 , 18 ]. As described above, SLE can involve the choroidal structures and blood flow and thus, leading to ischemia and atrophy in the retinal segments they supply with oxygen and nutrients [ 17 ]. In this context, our results could suggest that DLD, as a possible expression of choroidopathy, could be a sign of advancing disease [ 8 ].…”

“…When assuming that DLD are a sign of advancing disease, this finding stands in contrast with the known literature. Previous studies mostly state a thinning of the retinal layers in patients diagnosed with SLE compared to healthy controls nota bene [ 17 , 19 , 20 ]. Liu et al reason, that this thinning is due to vasculitis with subsequent atrophy in the ganglion cell layer [ 20 ].…”

“…Dias-Santos et al suggest there is retinal neurodegeneration taking place in the course of SLE disease progression. However, the authors observed that the layer increases in thickness as SLE advances, justifying this with neuronal remodeling [ 17 ]. Investigated and discussed in more detail by Jones et al, who examined the development of neurodegeneration in the retina, illustrated that after initial retinal damage, as for example in retinis pigmentosa or AMD, cell death with loss of neurons, reactive unstructured neuritogenesis, reformation of new synaptic connections, and glial reaction come to pass [ 21 ].…”