The clinical and immunologic characteristics of the patients with SLE and control participants are summarized in
Table 1. There were no significant differences between patients with SLE and control subjects for age (
P = 0.670) and sex (
P = 0.442). The median (IQR) time from the initial diagnosis of SLE was 3.0 years (IQR = 2.0–10.0 years, range = 0.5–22 years). The median (IQR) SELENA-SLEDAI score was 4.0 (IQR = 2.0–6.0, range = 0–14). Fourteen of 39 (35.9%) patients had a SELENA-SLEDAI score equal to or greater than 6, indicative of moderate to high disease activity. At the time of examination, 32 (82%) patients were receiving hydroxychloroquine, 21 (54%) azathioprine, 19 (49%) corticosteroids, 9 (23%) mycophenolate mofetil, 7 (18%) rituximab, 2 (5%) cyclosporine, 2 (5%) cyclophosphamide, and 2 (5%) were receiving intravenous immunoglobulin infusion as monotherapy or in combination.
Representative CCM images of the central corneal subepithelial nerve plexus in a healthy subject and a patient with SLE are shown in
Figure 1. CNBD (
P = 0.003) and CNFL (
P = 0.019) were significantly lower, and the mature LC density (
P = 0.002) was higher, but corneal sensitivity (
P = 0.178), CNFD (
P = 0.198), and total (
P = 0.200) and immature (
P = 0.648) LC densities were comparable in patients with SLE compared to control subjects (
Fig. 2,
Table 2). Of the patients with SLE, 13 of 39 (33%) had central nervous system involvement and fulfilled the criteria for NP-SLE. Immature LC density was higher with no difference in the corneal nerve or other LC parameters in patients with and without NP-SLE (
Table 3). There was no significant difference in corneal sensitivity, corneal nerve, and LC parameters between subjects with (
n = 11 [28%]) and without lupus nephritis (
P > 0.05 for all;
Supplementary Table S1).
The median (IQR) value of Schirmer's test was 16.0 mm (IQR = 10.0–21.0 mm) in 5 minutes in patients with SLE. No significant differences were observed in any of the study parameters between subgroups of patients with a Schirmer score of 6–10 mm (
n = 10 [26%]) and those higher than 10 mm (
P > 0.05 for all;
Supplementary Table S2).
CNFD (P = 0.008), CNBD (P = 0.005), and CNFL (P = 0.005) were lower, with no difference in corneal sensitivity (P = 0.675) and total, mature, or immature LC densities (P = 0.740, P = 0.740, and P = 0.573, respectively) in patients with moderate to high disease activity (SELENA-SLEDAI ≥6, n = 14 [36%]) compared with patients with no or mild disease activity (SELENA-SLEDAI <6). The SELENA-SLEDAI scores correlated with CNFD (ρ = −0.319, P = 0.048) and CNFL (ρ = −0.373, P = 0.019), and total and immature LC densities correlated with CNBD (ρ = −0.319, P = 0.048, and ρ = −0.328, P = 0.041, respectively). Central corneal sensitivity correlated with CNBD (ρ = 0.336, P = 0.037) and CNFL (ρ = 0.411, P = 0.009). There were no significant correlations between CCM parameters and Schirmer test scores, 24-hour urine protein, spot urine protein, or the estimated glomerular filtration rate (eGFR; P > 0.05 for all).