RESUMEN
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 â¼10-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.
Asunto(s)
Síndromes de Ojo Seco/patología , Enfermedades de los Párpados/patología , Glándulas Tarsales/patología , Síndrome de Sjögren/complicaciones , Adulto , Anciano , Artritis Reumatoide/complicaciones , Estudios de Casos y Controles , Conjuntiva/patología , Córnea/patología , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/metabolismo , Enfermedades de los Párpados/etiología , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Masculino , Glándulas Tarsales/metabolismo , Persona de Mediana Edad , Lágrimas/metabolismoRESUMEN
OBJECTIVE: We hypothesize that androgen deficiency is a critical etiologic factor in the pathogenesis of aqueous-deficient and evaporative dry eye in Sjögren's syndrome (SS). We investigated whether women with SS have a deficiency in total androgens. We also examined whether these patients have elevated serum concentrations of estrogens. METHODS: Blood was drawn from women with primary and secondary SS and age matched controls, and analyzed for steroid concentrations by gas and liquid chromatography-mass spectrometry. RESULTS: Our results show that women with SS are androgen-deficient. Concentrations of 5-androstene-3beta,17beta-diol (5-diol), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), androsterone-glucuronide (ADT-G), and androstane-3a,17beta-diol-G (3alpha-diol-G) were all significantly reduced in SS sera relative to controls. In contrast, SS was not associated with significant alterations in the serum concentrations of testosterone, androstenedione, estrone, or 17beta-estradiol. These overall findings could not be attributed to the use of oral contraceptives or hormone replacement therapy, because the concentrations of 5-diol, DHEA, DHT, ADT-G and 3a-diol-G were also decreased in patients with SS compared to levels in control women who were not taking exogenous estrogens. CONCLUSION: Our results show that women with SS are androgen-deficient.
Asunto(s)
Andrógenos/deficiencia , Síndrome de Sjögren/metabolismo , Andrógenos/sangre , Estudios de Casos y Controles , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Persona de Mediana Edad , Concentración Osmolar , Síndrome de Sjögren/sangreRESUMEN
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.
Asunto(s)
Síndrome de Resistencia Androgénica/patología , Ojo/patología , Glándulas Tarsales/patología , Adulto , Síndrome de Resistencia Androgénica/complicaciones , Estudios de Casos y Controles , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/fisiopatología , Enfermedades de los Párpados/etiología , Enfermedades de los Párpados/patología , Enfermedades de los Párpados/fisiopatología , Femenino , Humanos , Masculino , Glándulas Tarsales/fisiopatología , Encuestas y Cuestionarios , Lágrimas/metabolismoRESUMEN
OBJECTIVE: We have recently discovered that women with primary and secondary Sjögren's syndrome are androgen-deficient. We hypothesize that this hormone insufficiency contributes to the meibomian gland dysfunction, tear film instability, and evaporative dry eye that are characteristic of this autoimmune disorder. If our hypothesis is correct, we predict: (1) that androgens regulate meibomian gland function, control the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer; and (2) that androgen deficiency, due to an attenuation in androgen synthesis (e.g., during Sjögren's syndrome, menopause, aging, complete androgen-insensitivity syndrome [CAIS] and anti-androgen use), will lead to meibomian gland dysfunction and evaporative dry eye. The following studies were designed to test these predictions. METHODS: Experimental procedures included clinical studies, animal models, and histological, biochemical, molecular biological, and biomedical engineering techniques. RESULTS: Our results demonstrate that: (1) androgens regulate the meibomian gland. This tissue contains androgen receptor mRNA, androgen receptor protein within acinar epithelial cell nuclei, and Types 1 and 2 5alpha-reductase mRNAs. Moreover, androgens appear to modulate lipid production and gene expression in mouse and/or rabbit meibomian glands; and (2) androgen deficiency may lead to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, tear film instability, and evaporative dry eye. Thus, we have found that anti-androgen therapy in men is associated with meibomian gland disease, a decreased tear film breakup time, and functional dry eye. Furthermore, we have discovered that androgen receptor dysfunction in women with CAIS is associated with meibomian gland changes and a significant increase in the signs and symptoms of dry eye. Of interest, we have also found that androgen deficiency is associated with significant and striking alterations in the neutral and polar lipid patterns of human meibomian gland secretions. CONCLUSIONS: Our findings show that the meibomian gland is an androgen target organ and that androgen deficiency may promote meibomian gland dysfunction and evaporative dry eye. Overall, these results support our hypothesis that androgen deficiency may be an important etiologic factor in the pathogenesis of evaporative dry eye in women with Sjögren's syndrome.