Corneal confocal microscopy: a novel biomarker of small fibre neuropathy in SLE

Small fibre neuropathy (SFN) is an under-recognised complication of SLE that contributes to chronic pain and reduced quality of life. We assessed the utility of corneal confocal microscopy (CCM) for identifying small fibre damage in SLE in relation to disease activity, neuropathic pain and quality of life.

Participants with SLE and healthy controls underwent CCM to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), corneal nerve fibre tortuosity (CNFT), inferior whorl length (IWL), Douleur Neuropathique 4 (DN4) Score, vibration perception threshold (VPT) and sudomotor function.

Participants with SLE (n=59; age 38.6±9.6 years; mean Systemic Lupus Erythematosus Disease Activity Index Score 3.4±4.2) had significantly lower CNBD (41.5±21.3 vs 72.1±29.4 branches/mm², p=0.0001) and CNFL (18.5±4.3 vs 24.2±4.4 mm/mm², p=0.0001) but comparable CNFD (31.7±7.1 and 34.0±6.9 fibres/mm², respectively, p=0.25), CNFT (15.0±4.0 and 14.3±3.1, respectively, p=0.55), and IWL (38.5±8.0 and 35.6±5.9 mm/mm², respectively, p=0.16) compared with healthy controls (n=17). Patients with SLE had a DN4 Score of 3.5±2.5 and elevated VPT (4.1±3.3 vs 2.8±0.7 V, p<0.01) but comparable sudomotor function of the hands and feet (p=0.28-0.42). Active SLE was associated with a lower CNBD/CNFD ratio (p<0.05). Patients with SLE associated with sustained neuropathic pain (17.2%) had significantly lower CNFD, CNFL and IWL than those with transient (p<0.05-0.0001) and recurrent (p<0.05-0.01) pain but comparable VPT (p=0.27) and sudomotor function (p=0.14). Reduced CNFL was associated with bodily pain, affecting quality of life (p<0.05).

This study demonstrates that CCM detects peripheral neurodegeneration in patients with SLE, which relates to disease activity, sustained neuropathic pain and quality of life. CCM may serve as a rapid non-invasive neuroimaging technique to identify SFN in SLE.