Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Autoimmune Rheumatic Diseases.

PURPOSE: To evaluate dry eye severity and ocular surface inflammation in autoimmune rheumatic diseases (ARDs). METHODS: Seventy-nine patients with ARDs were enrolled, including 26 patients with rheumatoid arthritis (RA), 33 patients with systemic lupus erythematosus (SLE), and 20 patients with primary Sjögren's syndrome (pSS). All patients underwent ocular surface evaluations, including ocular surface symptoms, signs, conjunctival impression cytology, and tear multicytokine detection. Systemic conditions, including disease duration, disease activity, and serological parameters, were also noted. RESULTS: SLE patients had the shortest disease duration, and nearly half of them had low disease activity, while RA patients and pSS patients had a relatively long disease duration, and approximately 90% of them had moderate or high disease activity. The incidence of dry eye and the levels of the proinflammatory tear cytokines in SLE were significantly lower than those in RA and pSS. However, ocular surface squamous metaplasia was more severe in SLE and pSS than in RA. Dry eye severity in all ARD patients was shown to be independent of disease activity, while Nelson's grades were positively correlated with disease duration in RA patients. Disease-related serological parameters were associated with tear proinflammatory cytokines in all ARD patients. CONCLUSIONS: Variable degrees of dry eye and immune-mediated ocular surface inflammation persist in different ARD patients. In addition to a well-known association between dry eye and pSS, dry eye is also commonly observed in SLE and RA patients. Therefore, there is a definite need for regular ophthalmologic evaluations and topical medications in all patients with ARDs.

Evaluation of Dry Eye Severity and Ocular Surface Inflammation in Patients with Pemphigus and Pemphigoid.

PURPOSE: To evaluate ocular surface involvement, tear cytokine levels, and histopathological changes in pemphigus and pemphigoid patients. METHODS: A total of 22 patients (15 pemphigus and 7 pemphigoids) and 21 non-diseased controls were enrolled in our study. All participants underwent ocular surface evaluation, which included ocular surface disease index test, slit lamp observation, dry eye-related examination, tear multicytokine analysis, and conjunctival impression cytology. RESULTS: Pemphigus and pemphigoid patients presented much more severe conjunctivochalasis, corneal epithelial defects, corneal opacity, symblepharon   and dry eye. Severe ocular surface squamous metaplasia and a significant increase of tear macrophage inflammatory protein-1beta, tumor necrosis factor-alpha, interleukin (IL)-1ß, IL -6, and IL-8 occurred in pemphigus and pemphigoid patients. CONCLUSIONS: Our results revealed that ocular surface inflammation and dry eye persist in most pemphigus and pemphigoid patients, and do not occur in parallel with the systemic course. Regular ophthalmological examinations and local anti-inflammatory should be provided for pemphigus and pemphigoid patients.

Ocular surface involvement and histopathologic changes in the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional study.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN. METHODS: Ten patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed. RESULTS: Ocular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13. CONCLUSIONS: Severe pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

Rapamycin antagonizes angiogenesis and lymphangiogenesis through myeloid-derived suppressor cells in corneal transplantation.

Rapamycin is an immunosuppressive drug that is widely used in the postsurgery management of transplantation. To date, the mechanism by which rapamycin reduces posttransplant neovascularization has not been fully understood. Given the original avascularity and immune privilege of the cornea, corneal transplantation is considered as an ideal model to investigate neovascularization and its effects on allograft rejection. Previously, we found that myeloid-derived suppressor cells (MDSC) prolong corneal allograft survival through suppression of angiogenesis and lymphangiogenesis. Here, we show that depletion of MDSC abolished rapamycin-mediated suppression of neovascularization and elongation of corneal allograft survival. RNA-sequencing analysis revealed that rapamycin dramatically enhanced the expression of arginase 1 (Arg1). Furthermore, an Arg1 inhibitor also completely abolished the rapamycin-mediated beneficial effects after corneal transplantation. Taken together, these findings indicate that MDSC and elevated Arg1 activity are essential for the immunosuppressive and antiangiogenic functions of rapamycin.

Evaluation and correlation analysis of ocular surface disorders and quality of life in autoimmune rheumatic diseases: a cross-sectional study.

OBJECTIVE: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. METHODS: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman's analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. RESULTS: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. CONCLUSION: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients.

Ocular surface disorders affect quality of life in patients with autoimmune blistering skin diseases: a cross-sectional study.

BACKGROUND: Autoimmune blistering skin diseases (AIBD) are a group of rare chronic autoimmune diseases which are associated with ocular surface diseases especially dry eye disease. This study is designed to investigate the relationship between ocular surface disorders and quality of life among patients with autoimmune blistering skin diseases. METHODS: Twenty-four AIBD patients (18 pemphigus and 7 pemphigoid) and twenty-five non-AIBD controls were included. Ocular surface disease index (OSDI), ocular surface evaluation, including slit-lamp examination, Schirmer I test, tear break-up time, corneal fluorescein staining, lid-parallel conjunctival folds, meibomian gland evaluation, presence of symblepharon and corneal opacity were assessed. Life quality was evaluated by multiple questionnaires, including Medical Outcomes Study 36-Item Short Form Questionnaire (SF-36), Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Ocular surface tests and quality of life were compared between AIBD patients and non-AIBD controls. In the AIBD patients, the associations between ocular surface parameters and quality of life were also evaluated. RESULTS: 92% of AIBD patients and 87.5% of age- and sex-matched non-AIBD controls were diagnosed with dry eye in this study. Compared with non-AIBD controls, AIBD patients reported lower SF-36 scores (P < 0.05) and severer OSDI, Schirmer I test, tear break-up time, corneal fluorescein staining, presence of symblepharon and corneal opacity measures (P < 0.05). OSDI, Schirmer I test were correlated with SF-36 composite scores or scores on the SF-36 subscales. CONCLUSIONS: AIBD patients experience reduced quality of life and more severe ocular surface disorders including dry eye, symblepharon and corneal opacity. Early treatments of dry eye and collaborations among multidisciplinary physicians are necessary in patients with AIBD.

[Application of an intervention plan based on unplanned readmission risk model in the rehabilitation of patients with acute myocardial infarction complicated with cardiogenic shock after percutaneous coronary intervention].

OBJECTIVE: To study and analyze the application effect of intervention plan based on unplanned readmission risk model (LACE) in the rehabilitation of patients with acute myocardial infarction (AMI) complicated with cardiac shock (CS) after percutaneous coronary intervention (PCI). METHODS: Ninety-three patients with AMI complicated with CS who received PCI in Tianjin Union Medical Center from January 2019 to December 2020 were enrolled. The patients were divided into LACE intervention group (n = 46) and routine intervention group (n = 47) according to the different nursing intervention methods. The patients in the routine intervention group received routine interventions, including drug care, diet care, psychological care, health education and telephone follow-up, while those in the LACE intervention group were assessed for the risk of LACE, and then intervention measures were formulated according to the score of LACE index, including strengthening risk awareness, life behavior, daily life ability, self-care ability, health recovery and health needs. The follow-up period in both groups was 3 months. The changes of cardiac function, incidence of adverse cardiac events, readmission rate, self-management ability after intervention and quality of life level before and after intervention were compared between the two groups. RESULTS: There was no significant difference in cardiac function or quality of life before intervention between the two groups. After intervention for 3 months, the cardiac function and quality of life in the two groups were improved as compared with those before intervention. The left ventricular ejection fraction (LVEF) in the LACE intervention group was significantly higher than that in the routine intervention group (0.533±0.076 vs. 0.492±0.072, P < 0.05), the left ventricular end diastolic diameter (LVEDD) was significantly lower than that in the routine intervention group (mm: 47.09±7.01 vs. 53.23±7.15, P < 0.01), and the World Health Organization Quality of Life-brief (WHOQOL-BREF) score was also significantly higher than that in the routine intervention group (66.32±6.19 vs. 55.79±7.26, P < 0.01). The scores of self-management ability in the coronary heart disease self-management scale (CSMS) after intervention in the LACE intervention group were significantly higher than those in the routine intervention group (adverse hobbies score: 17.37±3.24 vs. 14.21±2.73, symptoms score: 14.82±3.11 vs. 10.56±2.65, emotional cognition score: 16.17±2.83 vs. 12.95±2.41, first aid score: 11.85±1.94 vs. 10.62±1.56, disease knowledge score: 15.58±2.73 vs. 12.68±2.61, daily life score: 17.80±2.61 vs. 14.33±2.36, treatment compliance score: 11.47±1.84 vs. 8.56±1.23, all P < 0.01). The incidence of adverse cardiac events and readmission rate in the LACE intervention group were significantly lower than those in the routine intervention group (10.87% vs. 29.79%, 4.35% vs. 17.02%, both P < 0.05). CONCLUSIONS: The intervention plan based on LACE risk model can effectively promote postoperative rehabilitation of patients with AMI complicated with CS after PCI, and also help to improve patients' self-management ability and quality of life, which is worthy of clinical promotion and application.

Myeloid-derived suppressor cells improve corneal graft survival through suppressing angiogenesis and lymphangiogenesis.

Myeloid-derived suppressor cells (MDSC) are one of the major negative regulators of immune responses during many pathological conditions such as cancer and transplantation. Emerging evidence indicates that MDSC also contribute to tumor progression through their pro-angiogenic activity in addition to immunosuppressive function. However, virtually nothing is known about the role of MDSC in the regulation of neovascularization after transplantation. Here we showed that antibody-mediated depletion of MDSC in mice led to robust growth of blood and lymphatic neovessels and rapid allograft rejection after corneal penetrating keratoplasty. In contrast, adoptive transfer of ex vivo generated MDSC from cytokine-treated bone marrow cells (evMDSC) suppressed neovascularization and prolonged corneal allograft survival in an inducible nitric oxide synthase (iNOS)-dependent manner. Mechanistically, compared to naïve MDSC control, evMDSC have increased expression of an anti-angiogenic factor thrombospondin 1 (Tsp-1) and decreased expression of two critical pro-angiogenic factors, vascular endothelial growth factor A (VEGF-A), and VEGF-C. These findings demonstrate MDSC as a critical anti-angiogenic regulator during transplantation. Our study also indicates that evMDSC are a valuable candidate agent for development of novel cell therapy to improve allograft survival after transplantation.

Corneal alteration and pathogenesis in diabetes mellitus.

The incidence of diabetes mellitus (DM) and its complications have increased considerably worldwide. Diabetic keratopathy is the major complication of the cornea characterized by delayed corneal wound healing, decreasing corneal epithelial sensitivity, and recurrent corneal ulcers. There is accumulating evidence that diabetic keratopathy is correlated with the hyperglycemic state. Different corneal components may produce different alterations under hyperglycemia. In addition, diabetic nerve alteration may become a novel biomarker of early-stage DM. Abnormalities of the corneal nerve plexus have been associated with diabetic inflammatory states. There is rapidly growing evidence based on investigations of diabetic corneal nerves through in vivo confocal microscopy. Understanding the molecular pathogenesis caused by hyperglycemia may assist in the identification of novel biomarkers, as well as therapeutic targets for early treatment. This review mainly summarizes recent findings on corneal alteration and pathogenesis in DM.