Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome.

PURPOSE: We hypothesized that women with primary (pSS) and secondary Sjögren syndrome (sSS; with systemic lupus erythematosus [SLE] or rheumatoid arthritis [RA]) have meibomian gland dysfunction (MGD). We sought to test our hypothesis. METHODS: Subjects with pSS, sSS + SLE, sSS + RA, and non-SS-related MGD were recruited from the Sjögren's Syndrome Foundation or outpatient clinics at Tufts University School of Dental Medicine or Brigham and Women's Hospital. The control population was recruited from the Greater Boston area. After providing written informed consent, the subjects underwent an eye examination and/or completed two questionnaires that assess symptoms of dry eye disease (DED). RESULTS: Our results demonstrate that pSS and sSS patients have MGD. These subjects had meibomian gland orifice metaplasia, an increased number of occluded meibomian gland orifices, and a reduced quality of meibomian gland secretions. Further, patients with pSS, sSS + SLE, sSS + RA, and MGD had significant alterations in their tear film, lid margin, cornea, and conjunctiva. Symptoms of DED were increased ∼10-fold in all pSS, sSS, and MGD groups relative to controls. CONCLUSIONS: Our findings support our hypothesis and show that individuals with pSS, sSS + SLE, and sSS + RA have MGD. In addition, our study indicates that patients with pSS and sSS have both aqueous-deficient and evaporative DED.

Safety of repeated topical ocular administration of a polycarbophil-based formulation in several models of ocular surgery in rabbits.

PURPOSE: To evaluate the safety of the polycarbophil-based formulation Durasite in rabbits when administered chronically to intact eyes and acutely to eyes compromised by a corneal epithelial defect, penetrating corneal incision, or laser in situ keratomileusis (LASIK) flap. The rheological properties were evaluated to characterize the behavior of the formulation on the ocular surface. SETTING: Bausch & Lomb, Rochester, New York, USA. DESIGN: Experimental study. METHODS: Intact eyes of albino rabbits received polycarbophil (0.6% or 1.3%) 3 times a day for 1 year. The compromised models using polycarbophil 0.9% were an epithelial defect, penetrating corneal incision, or LASIK flap. Eyes with the epithelial defects were dosed 10 times for 24 hours and then 2 times a day for 2 days, and the defect was monitored with fluorescein. The incision or LASIK eyes were dosed 4 times a day for 11 days starting the day before surgery, with 1 drop just before the surgical procedure. The eyes were examined microscopically. The rheological properties were evaluated using a controlled-stress rheometer with a synthetic tear fluid. RESULTS: No adverse ocular or systemic effects were observed with polycarbophil after chronic administration. In the compromised models, there were no adverse effects of the polycarbophil. There was no evidence of an anterior chamber reaction or qualitative effects on the corneal endothelium. Rheologically, the polycarbophil-based formulation behaved as a sheer-thinning fluid under physical conditions similar to the ocular surface. CONCLUSION: Results suggest that the polycarbophil-based formulation, like other shear-thinning formulations, is safe to use in topical ophthalmic pharmaceutical products indicated for chronic use and for treatment of conditions with compromise of the ocular surface.

A method to extract cytokines and matrix metalloproteinases from Schirmer strips and analyze using Luminex.

PURPOSE: The Schirmer's test is commonly used in the clinic for the diagnosis of dry eye disease by measuring tear volume. This report describes a procedure which can be used to recover tears from the Schirmer strip for the measurement of multiple tear cytokines as well as matrix metalloproteinases (MMPs) by Luminex technology. METHODS: Cytokine and MMP recovery was determined by using spiked Schirmer strips presoaked with known cytokines or MMPs prepared in PBS with 1% BSA. In a clinical study, tears were collected from 5 subjects using Schirmer strips. Strips were stored on ice immediately after removal from the subject and stored dry at -20 °C for 16-24 h. Cytokines were extracted from the Schirmer strip in 0.5 M NaCl with 0.5% Tween-20. Concentrations of cytokines and MMPs in collected tear samples were analyzed by Luminex using both a 10-cytokine and a 5-MMP kit. RESULTS: The standard curves for the assay in both the kit assay buffer and extraction buffer were identical for 9 of the 10 cytokines and all 5 MMPs. In the clinical sample all the cytokines (interleukin 1α [IL-1α], IL-1ß, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-13, monocyte chemotactic protein-1 [MCP-1], and tumor necrosis factor-α [TNF-α]) and 5 MMPs (MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10) tested were detected in at least 50% of the 10 subject samples. Recoveries from extracted Schirmer strips were >60% for 8 of the 10 cytokines and all MMPs. CONCLUSIONS: Numerous cytokines and MMPs were detected in the tear samples collected using the Schirmer strip, including many that have been implicated in ocular surface disease. This procedure may be used to evaluate the cytokine and MMP content in tear samples in clinical studies, especially for the evaluation of dry eye therapeutics. Because the Schirmer test is routine in the assessment of dry eye, this method offers the opportunity to evaluate both the quantity and quality of the tears.

Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?

PURPOSE: This study's purpose was to determine whether complete androgen insensitivity syndrome (CAIS) is associated with alterations in the meibomian gland and ocular surface. METHODS: Individuals with CAIS, as well as age-matched female and male controls, completed questionnaires which assessed dry eye symptoms and underwent slit lamp evaluations of the tear film, tear meniscus, lids and lid margins and conjunctiva. The quality of meibomian gland secretions was also analyzed. RESULTS: Our results demonstrate that CAIS is associated with meibomian gland alterations and a significant increase in dry eye signs and symptoms. Clinical assessment revealed that CAIS women, as compared to controls, had a significant increase in telangiectasia, keratinization, lid erythema and orifice metaplasia of the meibomian glands, and a significant decrease in the tear meniscus and quality of meibomian gland secretions. Questionnaire results showed that dry eye symptoms were increased over twofold in CAIS individuals, as compared to controls, including a significant increase in the sensations of dryness, pain and light sensitivity. CONCLUSION: Our results suggest that androgen insensitivity may promote meibomian gland dysfunction and an increase in the signs and symptoms of dry eye.

Complete androgen insensitivity syndrome: effect on human meibomian gland secretions.

OBJECTIVE: To determine whether androgen receptors affect the fatty acid profiles of neutral and polar lipids in human meibomian gland secretions. METHODS: Meibomian gland secretion samples were obtained from both eyes of (1) women with complete androgen insensitivity syndrome, a condition characterized by dysfunctional androgen receptors, and (2) age-matched female and male controls. Samples were processed for high-performance liquid chromatography, mass spectrometry, or both and for analysis of the mass spectra of neutral and polar lipid fatty acid fragment ions by 3 different methods. RESULTS: Androgen receptor dysfunction is associated with significant alterations in the appearance of numerous molecular species in the neutral and polar lipid fractions of meibomian gland secretions. The ability to detect these differences, and to assess their nature and extent, was facilitated by the use of several analytic approaches. Sex-related differences exist in the expression of a variety of neutral and, especially, polar fatty acid products in meibomian gland secretions. CONCLUSIONS: Androgens exert a significant effect on neutral and polar lipids in human meibomian gland secretions, and these hormonal effects may be mediated through androgen receptors.