Corneal subbasal nerve analysis in patients with primary Sjogren's syndrome: a novel objective grading method and clinical correlations

Purpose: To investigate corneal sub-basal nerve morphology changes in primary Sjogren's syndrome (SS) dry eye (SSDE) patients and determine the association with disease severity at microstructural level.

Methods: Twenty-eight eyes of 17 SSDE and 82 eyes of 47 age- and sex-matched non-SS dry eye (NSSDE) patients were included. The Ocular Surface Disease Index questionnaire (OSDI), Schirmer's test (ST), tear meniscus height (TMH), non-invasive breakup time (NIBUT), meibomian gland (MG) morphology, and ocular staining score (OSS) were assessed. In vivo confocal microscopy was performed to observe corneal sub-basal nerve morphology (length, reflectivity, width, and tortuosity). Associations between clinical features and nerve parameters were analysed.

Results: SSDE patients more frequently had increased nerve reflectivity (151.12 ± 17.07 vs. 139.37 ± 14.31 grey value), width (4.45 ± 0.87 vs. 3.92 ± 0.81 μm), tortuosity (132.90 ± 8.04 vs. 129.50 ± 7.33 degree), and higher reflectivity, width, and total nerve grades than NSSDE individuals (all P < 0.05). Significant associations were found between nerve reflectivity/width and anti-SSA [OR = 1.139 (1.013-1.281)/1.802 (1.013-4.465)]/labial gland biopsy [OR = 1.046 (1.002-1.161)/1.616 (1.020-3.243)]. Higher nerve width was associated with increased OSDI [β = 0.284 (0.187-0.455)], MG score [β = 0.185 (0.109-0.300)] and OSS [β = 0.163 (0.020-0.345)], but decreased NIBUT [β = - 0.247 (- 0.548 ~ - 0.154)]. Higher nerve total grade was associated with increased OSDI [β = 0.418 (0.157-0.793)] and OSS [β = 0.287 (0.027-0.547)], but decreased ST [β = - 0.410 (-0.857 ~ - 0.138)].

Conclusions: Corneal nerve morphology changes associated with clinical features in SS patients. These changes may facilitate severity evaluation and management of the disease.