Scheme of the analytical method.

<p>(1) Percent area of the ductal lumen per acinus. (2) Percent area of the acini per field (×200). (3) Size of the lacrimal gland acinar cell.</p

VDT duration.

<p>VDT duration, visual display terminals duration; VDT, VDT related to non-Sjögren's syndrome dry eye; SS, Sjögren's syndrome dry eye.</p

Clinical evaluation of ocular findings.

<p>VDT, VDT work related non-Sjögren's syndrome dry eye; SS, Sjögren's syndrome dry eye; LM, light microscopy; TEM, transmission electron microscopy; M, Male; F, Female; F, Fluorescein score; RB, Rose-Bengal score; BUT, Tear film break up time; S, Schirmer's test; S(N), Schirmer's test with nasal stimulation; VDT duration, Visual display terminals duration; h/day, hours per day; italics, These patients had been diagnosed as dry eye at the other institution and treated with eye drops.</p

Electron microscopic findings of the lacrimal gland acinus in the three groups.

<p>A: SV accumulation in the normal lacrimal gland (n = 4). Scale bars = 10 µm. B: Homogeneous SVs in normal controls. Scale bars = 5 µm. C: Excessive accumulation of SVs in the VDT group (n = 4). D: High magnification view of SVs in the VDT group. E: Only a few SVs in the SS group (n = 12). F: High magnification view of SVs in the SS group. G: Percent SV area per acinus. Total number of acini examined/group: 20/VDT group (4 cases), 58/SS group (12 cases), and 20/Normal controls (4 cases). *<i>P</i> = 0.021, ^†<i>P</i> = 0.004 (Mann-Whitney U test). H: SV diameter. Total number of vesicles examined/group: 6274/VDT group (4 cases), 11837/SS group (12 cases), and 2875/Normal controls (4 cases). **<i>P</i> = 0.025 (Mann-Whitney U test). Original magnification: ×2000 (A, C, E), ×5000 (B, D, F). Asterisk, Ductal lumen; Arrows, Nuclei; Triangle, SV.</p

Patient characteristics.

<p>VDT, VDT work related non-Sjögren's syndrome dry eye; SS, Sjögren's syndrome dry eye; M/W, man/woman; LE, light microscopy; TEM, transmission electron microscopy.</p

Hypothetical mechanism of dry eye in the VDT and SS groups.

<p>VDT, VDT work-related to non-Sjögren's syndrome dry eye; SS, Sjögren's syndrome dry eye.</p

Immunohistochemistry of VAMP8 and Rab3D.

<p>(A), (B): VAMP8 expression in normal controls was localized to the apical membrane of the lacrimal gland epithelia (A, B; 87 years old, Female). (C), (D): In the VDT group, strong VAMP8 immunostaining was present in the cytoplasm and basal side of the lacrimal gland epithelial cells but not at the apical membrane (C, D; VDT-case 3). (E), (F): VAMP8 staining in the SS group was seen close to the basal side of the acinar epithelia (E, F; SS-case 8). A, C, E; Original magnification: ×400, B, D, F; Magnified view of the acinus with asterisk in A, C, E. Scale bars = 20 µm. (G), (H): Rab3D expression in normal controls. Rab3D was expressed at the apical side of the cytoplasm in the lacrimal gland epithelia, but not at the apical membrane, where VAMP8 was expressed (G, H; 87 years old, Female). (I), (J): In the VDT group, strong Rab3D immunostaining was observed in the cytoplasm of the lacrimal gland epithelial cells (I, J; VDT-case 3). (K), (L): In the SS group, faint Rab3D expression was observed at the basal side of the acinar epithelia (K, L; SS-case 8). G, I, K; Original magnification: ×400. H, J, L: Magnified view of the acinus with asterisk in G, I, and K. Scale bars = 20 µm.</p

Lacrimal gland histology by H&E staining.

<p>(A) H&E staining of lacrimal gland from normal controls (n = 9). (B) H&E staining of lacrimal gland from the VDT group (n = 4). (C) H&E staining of lacrimal gland from the SS group (n = 13). Arrows indicate ductal lumens. Circle indicates one acinus. Scale bars = 50 µm. (D) Percent area of the ductal lumen per acinus. Total number of acini examined/group: 879/VDT group (4 cases), 2241/SS group (13 cases), and 1869/Normal controls (9 cases). *<i>P</i> = 0.03, <b>^†</b><i>P</i> = 0.013 (Mann-Whitney U test). (E) Percent area of the acini per field. Number of fields/group: 12/VDT group (4 cases), 39/SS group (13 cases), and 27/Normal controls (9 cases). **<i>P</i> = 0.001, <b>^††</b><i>P</i> = 0.013 (Mann-Whitney U test). (F) Acinar cell size relative to that of normal acinar cells. Number of cells measured/group: 6668/VDT group (4 cases), 19021/SS group (13 cases), and 17325/Normal controls (9 cases). ***<i>P</i> = 0.01 (Mann-Whitney U test). Original magnification: ×200 (A–C).</p