Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.
Male ; Humans ; Aged ; Anemia, Hemolytic, Autoimmune/diagnosis* ; Sjogren's Syndrome/diagnosis* ; Anemia, Hemolytic/complications* ; Dry Eye Syndromes/complications* ; Autoantibodies

OBJECTIVE: To explore the effect of hypothyroidism (HT) on the ocular surface status of patients with primary Sjögren's syndrome-related dry eye (pSS-DED). METHODS: The cross-sectional study included 36 patients with pSS-DED who were treated at the dry eye clinic of Peking University Third Hospital from December 2020 to June 2021, of whom 12 were pSS-DED patients combined with HT. In the same period, 24 patients with simple dry eye disease (DED) were served as a control group. All the patients filled out the Ocular Surface Disease Index (OSDI) questionnaire, and performed tear film break-up time (BUT), Schirmer test, tear meniscus height, corneal/conjunctival fluorescein staining, meibomian gland secretion capacity, meibum evaluation and confocal microscope examination. RESULTS: (1) Compared with pSS-DED and simple DED patients, pSS-DED +HT patients had lower average BUT [(2.7±0.8) s], Schirmer test [(4.9±4.8) mm] and tear meniscus height [(0.13±0.03) mm], and the difference was statistically significant (F=12.43, P < 0.01; F=6.96, P < 0.01; F=3.31, P < 0.05). (2) Compared with DED and pSS-DED patients, the meibomian gland secretion capacity and meibomian trait scores of pSS-DED+HT patients were mainly distributed in the high division. There were statistically significant differences in the distribution of secretion capacity of meibomian glands (χ²=10.72, P < 0.05) and meibomian trait assessment scores (χ²=8.34, P < 0.05) among the three groups. (3) Serum total thyroxine and serum free thyroxine levels in the pSS-DED+HT patients showed positive correlation (P < 0.05, P < 0.05) with their BUT (r=0.60, 0.60), Schirmer's test (r=0.64, 0.66) and tear river height (r=0.61, 0.62), independent of lid gland secretory capacity; no significant correlation was found between thyroid-stimulating hormone, anti-thyroglobulin antibody and lid gland secretory capacity. Thyroid hormone, anti-thyroglobulin antibody, and thyroid peroxidase antibody were not found to be significantly correlated with ocular surface status. (4) Compared with pSS-DED, the fiber density of the subbasal nerve plexus in pSS-DED+HT group decreased (t=2.06, P < 0.05), and the curvature score increased (t=2.13, P < 0.05). CONCLUSION The ocular surface condition of pSS-DED patients with HT is worse than that of pSS-DED and DED patients. The main manifestations are that tear secretion, tear film stability, secretory function of the meibomian glands, meibum trait and fiber density of the subbasal nerve plexus decrease while the curvature increases. The mechanism might be related to the decrease in thyroid hormone production.
Cross-Sectional Studies ; Dry Eye Syndromes/etiology* ; Humans ; Hypothyroidism/complications* ; Sjogren's Syndrome/complications* ; Thyroxine

PURPOSE: To report a case of a SmartPlug that partially extruded through the canalicular mucosa. CASE SUMMARY: A 62-year-old female patient visited our Department of Ophthalmology for redness and discharge in her right eye that began worsening a week prior. The patient was diagnosed with severe dry eye syndrome via Sjogren's syndrome. The SmartPlug was inserted into her left lower punctum 12 years prior, and another plug was inserted in the right 9 years prior. Nothing notable was found in her history. The best corrected visual acuity and intraocular pressure at the initial visit was 1.0 and 14 mmHg, respectively, in both eyes. Swelling, erythema, and tenderness at the right lower punctum were identified. As we irrigated the lower lacrimal system, partial obstruction was suspected and a large amount of mucopurulent discharge in the conjunctival fornix with conjunctival injection was seen. Under the right lower punctum, a 1 × 1 mm yellowish foreign body was partially extruding from the canalicular mucosa. The foreign body was removed, and a round defect was left. The patient's symptom completely resolved after 4 weeks of topical antibiotics and ointment treatment. CONCLUSIONS: In patients who have a SmartPlug inserted prior to visits for redness and discharge, a SmartPlug plug extrusion should be considered.
Anti-Bacterial Agents ; Dry Eye Syndromes ; Erythema ; Female ; Foreign Bodies ; Humans ; Intraocular Pressure ; Middle Aged ; Mucous Membrane* ; Ophthalmology ; Sjogren's Syndrome ; Visual Acuity

The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028).
Aged ; B-Cell Activating Factor/analysis/blood ; Blood Sedimentation ; Double-Blind Method ; Drug Administration Schedule ; Dry Eye Syndromes/complications/*drug therapy ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hydroxychloroquine/*therapeutic use ; Interleukin-16/analysis/blood ; Interleukin-17/analysis/blood ; Male ; Middle Aged ; Placebo Effect ; Prospective Studies ; Sjogren's Syndrome/*complications/diagnosis ; Th17 Cells/cytology/immunology ; Treatment Outcome

Dry eye syndrome (DES) is recognized as a public health concern. One of the pathophysiologies in the development of DES is inflammation, and metabolic syndrome (MetS), which is highly prevalent in the general population, is a well-known chronic and systemic inflammatory condition. Despite the increasing interest regarding a relationship between DES and MetS, information is lacking on the association between DES and MetS and its individual components. We investigated the association between DES symptoms and MetS and its components among adults aged ≥ 19 years using population-based data from the Korea National Health and Nutrition Examination Survey V. A sample group of 15,294 adults (42.67% men and 57.33% women) completed household interviews in which they provided blood (for high-density lipoprotein cholesterol, triglyceride, and glucose) and anthropometric measurements (including waist circumference, weight, and height) to define MetS. We also collected information regarding sociodemographic and behavioral risk factors. The survey results showed that 11.50% of men and 22.35% of women experienced DES and 5.30% of patients had both DES and diagnosis of MetS, including 204 men and 606 women. Thus, no significant difference was observed between DES and the diagnosis of MetS according to sex (P = 0.4008 in men; P = 0.0804 in women); however, a significant association was observed between DES and hypertriglyceridemia in women (OR, 1.13; 95% CI, 1.01-1.29). Therefore, hypertriglyceridemia might be an important factor in the association between DES and MetS. Further longitudinal research is needed to evaluate this relationship.
Adult ; Aged ; Blood Glucose/analysis ; Body Height ; Body Weight ; Cholesterol, HDL/blood ; Cross-Sectional Studies ; Dry Eye Syndromes/complications/*diagnosis/epidemiology ; Female ; Humans ; Hypertriglyceridemia/complications/diagnosis ; Interviews as Topic ; Male ; Metabolic Syndrome X/complications/*diagnosis/epidemiology ; Middle Aged ; Nutrition Surveys ; Prevalence ; Republic of Korea/epidemiology ; Risk Factors ; Sex Factors ; Triglycerides/blood ; Waist Circumference ; Young Adult

This retrospective study was performed to analyze the long-term outcome of topical corticosteroid treatment for severe dry eye associated with Sjogren's syndrome (SS). Patients who had severe dry eye associated with SS were topically treated with loteprednol etabonate 0.5% (group A, n=66) or fluorometholone 0.1% (group B, n=67) twice daily and were followed up for 2 years. Visual acuity (VA), intraocular pressure (IOP), Schirmer test, tear film breakup time (BUT), keratoepitheliopathy, and symptom scores were measured at baseline and 6, 12, 18, and 24 months after treatment. VA and IOP were not changed significantly during follow-up in either group. Schirmer test results, keratoepitheliopathy, and symptom scores at 6, 12, 18, and 24 months (p<0.05) and tear film BUT at 12, 18, and 24 months (p<0.05) significantly improved after treatment compared with baseline in both groups. No significant differences between the groups were found in any parameter during follow-up. At 24 months, the number of patients with IOP elevation of more than 2 mmHg compared with baseline was 4 in group A (6.1%) and 9 in group B (13.4%). The mean IOP in these patients was lower in group A than in group B (15.00+/-0.82 mmHg versus 16.50+/-1.12 mmHg; p=0.04). Long-term application of low-dose topical corticosteroids is effective for controlling signs and symptoms of chronic, severe dry eye associated with SS. Loteprednol etabonate 0.5% may have a lower risk for IOP elevation than fluorometholone 0.1%.
Adrenal Cortex Hormones ; Dry Eye Syndromes ; Fluorometholone ; Follow-Up Studies ; Humans ; Intraocular Pressure ; Retrospective Studies ; Sjogren's Syndrome ; Tears ; Visual Acuity ; Loteprednol Etabonate

PURPOSE: To investigate the prevalence and clinical aspects of Sjogren syndrome in patients who were diagnosed with dry eye syndrome in Korea. METHODS: The medical records of patients who were diagnosed with dry eye syndrome in a dry eye clinic during a 2-year period (March 2008 to March 2010) and were followed up for more than 3 months were reviewed retrospectively. RESULTS: A total of 206 patients were included in the present study. Fifty-eight patients (28%) had Sjogren syndrome and 39 patients (19%) showed primary Sjogren syndrome. Sjogren syndrome patients showed poorer results than non-Sjogren syndrome patients in ocular surface disease index score (OSDI), tear break up time, Schirmer test score, and ocular surface staining score using the Oxford scheme (p < 0.05). Among the patients with primary Sjogren syndrome, 27 patients were SSA (anti-Ro antibodies) or SSB (anti-La antibodies) positive and 12 patients were sero-negative. There were no statistically significant differences in objective or subjective parameters between the sero-positive and sero-negative groups. CONCLUSIONS: Sjogren syndrome was observed in 28% of all dry eye patients, in two-thirds of severe dry eye patients. Sjogren syndrome patients showed more severe clinical aspects than dry eye patients with non-Sjogren syndrome. Diagnosing Sjogren syndrome through systemic evaluation is necessary in the patients with severe dry eye.
Autoantibodies ; Dry Eye Syndromes ; Eye ; Humans ; Medical Records ; Prevalence ; Sjogren's Syndrome ; Tears

Recently, the association of Th-17 cells or IL-17 with ocular inflammatory diseases such as uveitis, scleritis and dry eye syndrome was discovered. We assessed whether interleukin (IL)-17 was present in the tears of various ocular surface inflammatory diseases and the tear IL-17 concentrations were clinically correlated with various ocular surface inflammatory diseases. We measured concentrations of IL-17 in tears of normal subjects (n = 28) and patients (n = 141) with meibomian gland dysfunction (MGD), dry eye syndrome (DES), Sjogren syndrome (SS), Stevens-Johnson syndrome (SJS), graft-versus-host disease (GVHD), filamentary keratitis, and autoimmune keratitis associated with rheumatoid arthritis or systemic lupus erythematosus. Clinical epitheliopathy scores were based on the surface area of corneal and conjunctival fluorescein staining. The mean concentrations of IL-17 in tears of patients with filamentary keratitis, GVHD, autoimmune keratitis, SS, DES, MGD, SJS were significantly higher in order than that in normal subjects. Tear IL-17 concentration was significantly correlated with clinical epitheilopathy scores in the patients with systemic inflammatory disease, while tear IL-17 was not correlated with clinical severity of the cornea and conjunctiva in the dry eye patients without any systemic inflammatory disease. Tear IL-17 is likely to correlate clinically with corneal disease severity only in the patients with systemic inflammatory disease.
Adult ; Aged ; Dry Eye Syndromes/*metabolism ; Eye Diseases/diagnosis/*metabolism ; Eyelid Diseases/metabolism ; Female ; Graft vs Host Disease/metabolism ; Humans ; Interleukin-17/*analysis ; Keratitis/metabolism ; Male ; Meibomian Glands/physiopathology ; Middle Aged ; Severity of Illness Index ; Sjogren's Syndrome/metabolism ; Stevens-Johnson Syndrome/metabolism ; Tears/metabolism

PURPOSE: To investigate the clinical usefulness of conjunctival brush cytology (CBC) in the diagnosis of dry eye syndrome. METHODS: Conjunctival impression cytology (CIC) was performed on the right eye and CBC was performed on the left eye in 24 patients with dry eye syndrome (9 patients with Sjogren's syndrome (SS) and 15 patients with non-Sjogren syndrome (Non-SS)) and 7 control subjects. The grade of squamous metaplasia was analyzed and the correlation between the grade and tear surface parameters was evaluated. RESULTS: The squamous metaplasia grade score in CIC and CBC were 2.44+/-0.73 and 1.56+/-1.01 in SS patients (p=0.047), 1.53+/-0.74 and 0.80+/-0.78 in Non-SS patients (p=0.017), and 0.43+/-0.54 and 0.14+/-0.38 (p=0.250) in control subjects, respectively. In SS patients, the score correlated significantly with the symptom score, basal tear secretion, break-up time (BUT) and keratoepitheliopathy score in CBC (p<0.05), but did not correlate with the tear surface parameters in CIC. In Non-SS patients, the score correlated significantly with the symptom score, basal tear secretion, BUT and keratoepitheliopathy score in CBC, and with the keratoepitheliopathy score in CIC (p<0.05). CONCLUSIONS: CBC is a more useful method than CIC in the diagnosis of dry eye syndrome.
Dry Eye Syndromes ; Eye ; Humans ; Metaplasia ; Sjogren's Syndrome ; Tears

PURPOSE: This study was performed to evaluate the level of I-TAC in tears of patients with dry eye syndrome and its correlation with the tear surface parameters. METHODS: I-TAC levels were measured by enzyme-linked immunosorbent assay (ELISA) in tear samples collected from 33 dry eye patients (16 patients with Sjogren syndrome and 17 patients with non-Sjogren syndrome) and 15 control subjects. The correlations between I-TAC levels and tear surface parameters including tear film break-up time (BUT), basal tear secretion, tear clearance rate (TCR), corneal sensation, keratoepitheliopathy and conjunctival goblet cell density were analyzed. RESULTS: The mean levels of I-TAC were 717+/-377 pg/ml in patients with dry eye and 444+/-119 pg/ml in control subjects (P=0.003). The mean levels in Sjogren syndrome patients (1261+/-324 pg/ml) were significantly higher than those of non-Sjogren syndrome patients (614+/-131 pg/ml, P=0.003). I-TAC levels correlated significantly with basal tear secretion (P=0.006), TCR (P=0.007), keratoepitheliopathy (P=0.022) and goblet cell density (P<0.001), but did not correlate with BUT (P=0.110) and corneal sensation (P=0.090). CONCLUSIONS: The level of I-TAC is elevated in tears of patients with dry eye syndrome including Sjogren syndrome. The level correlates with disease severity and tear surface parameters.
Dry Eye Syndromes ; Enzyme-Linked Immunosorbent Assay ; Eye ; Goblet Cells ; Humans ; Sensation ; Sjogren's Syndrome ; Tears