Evaluation of patients with dry eye for the presence of primary or secondary Sjӧgren’s syndrome

Figures & data

Figure 1 Flowchart for inclusion of dry-eye patients to be included in the study to diagnose Sjӧgren’s syndrome.

Abbreviations: TBUT, tear-film breakup time; OSS, ocular staining score; RF, rheumatoid factor; ANA, antinuclear antibody.

Figure 2 Ocular staining score (OSS). (A) OSS with rose bengal dye giving a score >3. (B) OSS with rose bengal dye giving a score <3.

Figure 3 H&E-stained labial salivary glands (LSGs).

Notes: (A) LSGs with three variously sized lymphocytic foci. The entire specimen had a focus score >1/4 mm² (original magnification 40×). (B) Normal-appearing acini immediately adjacent to the lymphocytic foci (original magnification 100×). (C) LSGs show small lymphocytic aggregate (FLS) that is minimally sized (>50 cells) for inclusion in a focusscore calculation (original magnification 200×).

Figure 4 H&E-stained labial salivary glands (LSGs).

Notes: (A) LSGs exhibiting nonspecific chronic sialadenitis with scattered lymphocytes and plasma cells (original magnification 100×). (B) LSGs exhibiting normal glands (original magnification 40×).

Table 1 Characteristics of dry-eye patients studied​

	Group I: ophthalmology clinic cohort (n=23)	Group II: rheumatology clinic cohort (n=35)	t/U/χ^2	P-value
Age, years, mean (SD)	44.2 (14.3)	45.1 (9.9)	−0.263	0.794
Sex  Male, n (%)  Female, n (%)	3 (13%) 20 (87%)	3 (8.6%) 32 (91.4%)	0.299^b	0.673
Dry eye, n (%)	23 (100%)	35 (100%)	0	0
Dry-eye duration, years, median/IQR	1/(0.3–2)	1/(0.3–3)	388	0.816
Dry mouth, n (%)	20 (87%)	29 (82.9%)	0.178^b	1
Dry-mouth duration, years, median/IQR	1/(0.2–2.8)	1/(0.2–2)	264	0.593
Salivary-gland enlargement, n (%)	2 (8.7%)	3 (8.6%)	0 ^(b)	1
Schirmer test I  <5 mm, n (%)  5–10 mm, n (%)	3 (13%) 20 (87%)	9 (25.7%) 26 (74.3%)	1.358^b	0.329
TBUT  <5 seconds, n (%)  5–10 seconds, n (%)	9 (39.1%) 14 (60.9%)	16 (45.7%) 19 (54.3%)	0.245^a	0.620
OSS  ≥3, n (%)  <3, n (%)	4 (17.4%) 19 (82.6%)	4 (11.4%) 31 (88.6%)	0.415^b	0.700
ANAs, n (%)	1 (4.3%)	1 (2.9%)	0.093^b	1
RF, n (%)	0	12 (34.3%)	9.943^b	0.002*
Anti-SSA/Ro, n(%)	1 (4.3%)	0	1.548^b	0.397
Anti-SSB/La, n (%)	0	0	0	0
Histopathology of LSGB  FLS (focus score ≥1)  FLS (focus score <1)  Chronic nonspecific sialadenitis  Normal	n=3 2 (66.7%) 1 (33.3%) 0 0	n=4 0 2 (50%) 1 (25%) 1 (25%)	4.273^b	0.486

Notes: Parametric quantitative data expressed as means (SD) and nonparametric quantitative data expressed as medians (IQR), while qualitative data are expressed as numbers and percentages. Independent-sample t-tests for parametric quantitative data between the two groups; Mann–Whitney U test for nonparametric quantitative data between the two groups. ^aχ² test (if expected value within cell >5); ^bFisher’s exact test (if expected value within cell <5) for qualitative data between the two groups. *P<0.05.

Abbreviations: OSS, ocular staining score; TBUT, tear-film breakup time; ANAs, antinuclear antibodies; RF, rheumatoid factor; FLS, focal lymphocytic sialadenitis; LSGB, labial salivary–gland biopsy.

Figure 5 Diagnostic flow of study in Sjӧgren’s syndrome patients.

Abbreviations: OSS, ocular staining score; FLS, focal lymphocytic sialadenitis; NSCS, nonspecific chronic sialadenitis.

Table 2 Comparisons of ocular tests, autoantibodies, and LSGB with Sjӧgren’s syndrome

		Sjӧgren's		P-value
		Negative	Positive
		n=55	n=3
Schirmer test	5–10 mm <5 mm	46 (83.6%) 9(16.4%)	0 3 (100%)	0.007*
TBUT	5–10 sec <5 sec	31 (56.4%) 24(43.6%)	2(66.7%) 1 (33.3%)	1
OSS	<3 >3	50 (90.9%) 5(9.1%)	0 3 (100%)	0.002*
RF	Negative Positive	43 (78.2%) 12(21.8%)	3(100%) 0	1
ANAs	Negative Positive	53 (96.4%) 2(3.6%)	3(100%) 0	1
Anti-SSA/Ro	Negative Positive	55 (100%) 0	2(66.7%) 1 (33.3%)	0.052
LSGB	Negative Positive	n=5 5 (100%) 0	n=2 0 2 (100%)	0.048*

Notes: Qualitative data expressed as numbers and percentages. Fisher’s exact test (if expected value within cell <5) for qualitative data between the two groups. *P<0.05.

Abbreviations: TBUT, tear-film breakup time; OSS, ocular staining score; RF, rheumatoid factor; ANAs, antinuclear antibodies; LSGB, labial salivary–gland biopsy.

Table 3 Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ocular tests, autoantibodies and LSGB for diagnosis of Sjӧgren’s syndrome

	Sensitivity	Specificity	PPV	NPV	Accuracy
Schirmer test <5 mm	100%	83.6%	25%	100%	84.5
TBUT <5 seconds	33.3%	56.4%	4%	93.9%	55.2
OSS ≥3	100%	90.9%	37.5%	100%	91.4
RF	0	78.2%	0	93.5%	74.1
ANAs	0	96.4%	0	94.6%	91.4
Anti-SSA/Ro	33.3%	100%	100%	96.5%	96.6
LSGB	100%	100%	100%	100%	100

Abbreviations: PPV, positive predictive value; NPV, negative predictive value; TBUT, tear-film breakup time; OSS, ocular staining score; RF, rheumatoid factor; ANAs, antinuclear antibodies; LSGB, labial salivary–gland biopsy.

Table 4 Correlations between ocular tests, autoantibodies, LSGB, and Sjӧgren’s syndrome

	Sjӧgren’s syndrome
	r	P-value
Schirmer test	0.457	<0.001*
TBUT	−0.046	0.731
OSS	0.584	<0.001*
RF	−0.119	0.372
ANAs	−0.044	0.742
Anti-SSA/Ro	0.567	<0.001*
LSGB	0.828	<0.001*

Notes: Nonparametric Spearman’s ρ correlation. *P<0.05.

Abbreviations: TBUT, tear-film breakup time; OSS, ocular staining score; RF, rheumatoid factor; ANAs, antinuclear antibodies; LSGB, labial salivary–gland biopsy.