Dry Eyes Abstracts 1

© 2012

Testosterone for Dry Eyes

         Dach 2010 Download

Total testosterone level in postmenopausal women with dry eye

         (Duarte, Pinto et al. 2007) Download

PURPOSE: The purpose of this study was to compare total testosterone blood level among three groups of postmenopausal women: control, mild to moderate dry eye and severe dry eye. METHODS: Twenty-nine postmenopausal women were selected. The exclusion criteria were: hormone replacement therapy in the last 8 weeks, mechanical palpebral abnormalities, pterygium, lacrimal obstructions, intraocular inflammation or contact lens use. A blood sample was collected for total testosterone level determination, and the patients were submitted to an ophthalmologic examination (emphasizing on dry eye detection) and answered the OSDI (Ocular Surface Disease Index) questionnaire. Five patients were excluded. Postmenopausal women were divided into three groups according to OSDI score and the ophthalmic examination. RESULTS: Five patients were classified in the no dry eye group (control), fifteen in the mild to moderate dry eye group and four in the severe dry eye group. There were no statistically significant differences regarding mean age (p=0.3915); instruction level (p=0.9333); number of comorbidities (p=0.2551); medication taken (p=0.2844) and total testosterone level among those groups (p=0.1275). CONCLUSION: Further research with a greater bigger sample is necessary to establish the relation of androgen levels in dry eye patients.

Dry eye in post-menopausal women using hormone replacement therapy

         (Erdem, Ozdegirmenci et al. 2007) Download

PURPOSE: To evaluate the effect of hormone replacement therapy (HRT) on dry eye in post-menopausal women. METHODS: Forty post-menopausal women with dry eye (20 patients, group 1) and without dry eye (20 patients, group 2), and planning to receive HRT (estrogen plus progesterone), were recruited as the study groups. Forty age-matched untreated women were enrolled as controls (group 3 with dry eye, 5 patients; group 4 without dry eye, 35 patients). Patients having at least one of the symptoms (dryness, itching, photophobia, foreign body sensation, and tearing) together with two of the tests with positive results for dry eye (tear film break-up time (BUT), fluorescein staining of the cornea, analysis of the meibomian gland, and Schirmer I test) in both eyes were considered dry eye positive. Hormonal assay for follicle stimulating hormone, luteinizing hormone, estradiol, and free testosterone was performed. Dry eye statuses in the groups were evaluated statistically. RESULTS: Four patients with incomplete follow-up data were excluded. HRT use increased estradiol levels in the groups. Mean ages of patients (50.2+/-4.8 and 50.7+/-3.9 years, and 50.0+/-4.6 and 53.0+/-3.9 years) were similar (p=0.67). Duration of menopause in groups 1 and 2 (3.2+/-2.2 and 1.4+/-1.2 years; p=0.01), and in groups 3 and 4 (3.0+/-1.6 and 1.7+/-1.3 years; p=0.014) were different. At the third month examinations, all of the patients in group 1, and 11 patients (61.1%) in group 2 had dry eye (p=0.003). CONCLUSION: Duration of menopause and use of HRT may increase the incidence of dry eye in post-menopausal woman.

Androgen Deficiency in Ocular Surface Disease

         Farjo 2009 Download

Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction

            (Goto, Shimazaki et al. 2002) Download

OBJECTIVE: We developed low-concentration homogenized castor oil eye drops for the treatment of patients with noninflamed obstructive meibomian gland dysfunction (MGD), a major cause of lipid-deficiency dry eye, and assessed the safety, stability, and efficacy of the eye drops. DESIGN: Randomized, double-masked, placebo-controlled crossover clinical trial. PARTICIPANTS: Forty eyes of 20 patients with noninflamed MGD. METHODS: After a preliminary study of eye drops containing castor oil, 2% castor oil and 5% polyoxyethylene castor oil (emulsifier) were mixed to formulate homogenized oil eye drops. The patients were assigned randomly to receive oil eye drops or placebo six times daily for 2 periods of 2 weeks each. MAIN OUTCOME MEASURES: At the end of each treatment period, we assessed symptoms, tear interference grade, tear evaporation, fluorescein and rose bengal scores, tear break-up time (BUT), and meibomian gland orifice obstruction. Safety and stability tests were also performed. RESULTS: Symptom scores, tear interference grade, tear evaporation test results, rose bengal scores, tear BUT, and orifice obstruction scores after the oil eye drop period showed significant improvement compared with the results after the placebo period. No complications attributable to the eye drops were observed. The oil eye drops were stable when stored at 4 degrees C. CONCLUSIONS: The results indicate that castor oil eye drops are effective and safe in the treatment of MGD. The possible mechanisms of this treatment are improvement of tear stability as a result of lipid spreading, ease of meibum expression, prevention of tear evaporation, and the lubricating effect of the oil eye drops.

Androgen regulation of gene expression in human meibomian gland and conjunctival epithelial cells

            (Khandelwal, Liu et al. 2012) Download

PURPOSE: Androgens exert a significant influence on the structure, function and/or pathophysiology of the meibomian gland and conjunctiva. We sought to determine whether this hormone action involves the regulation of epithelial cell gene expression in these tissues. METHODS: Immortalized human meibomian gland and conjunctival epithelial cells were treated with placebo or dihydrotestosterone (DHT) and processed for molecular biologic procedures. Gene expression was evaluated with BeadChips and data were analyzed with bioinformatic and statistical software. RESULTS: Androgen treatment significantly influenced the expression of approximately 3,000 genes in immortalized human meibomian gland and conjunctival epithelial cells. The nature of DHT action on gene activity was predominantly cell-specific. Similarly, DHT exerted a significant, but primarily cell-specific, influence on many gene ontologies and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These included groups of genes related, for example, to lipid dynamics, innate immunity, cell cycle, Janus kinase (JAK)-signal transducer and activator of transcription (stat) cascades, oxidative phosphorylation, the proteasome, and mammalian target of rapamycin (mTOR), Wnt, and peroxisome proliferator-activated receptor (PPAR) signaling. CONCLUSIONS: Our findings support our hypothesis that androgens regulate gene expression in human meibomian gland and conjunctival epithelial cells. Our ongoing studies are designed to determine whether many of these genes are translated and play a role in the health and well being of the eye.

The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland

            (Knop, Knop et al. 2011) Download

Effect of androgen deficiency on the human meibomian gland and ocular surface

            (Krenzer, Dana et al. 2000) Download

The purpose of this study was to determine whether the chronic use of antiandrogen medications leads to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, decreased tear film stability, and evaporative dry eye. Subjects taking antiandrogen therapy for prostatic indications, as well as age-related controls, were asked to complete a questionnaire that assessed dry eye symptoms and then were given a complete anterior segment examination. Moreover, meibomian gland secretions were obtained from each eye and analyzed by high-performance liquid chromatography/mass spectrometry for the relative content of cholesterol, cholesterol esters, wax esters, diglycerides, triglycerides, and specific molecular species in the diglyceride fraction. Our results demonstrate that patients taking antiandrogen treatment, compared with age-related controls, had a: 1) significant increase in the frequency of appearance of tear film debris, an abnormal tear film meniscus, irregular posterior lid margins, conjunctival tarsal injection, and orifice metaplasia of the meibomian glands; 2) significant increase in the degree of ocular surface vital dye staining; 3) significant decrease in the tear film breakup time and quality of meibomian gland secretions; and 4) significant increase in the frequency of light sensitivity, painful eyes, and blurred vision. In addition, the use of antiandrogen pharmaceuticals was associated with significant changes in the relative amounts of lipids in meibomian gland secretions. Our findings indicate that chronic androgen deficiency is associated with meibomian gland dysfunction and dry eye.

The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis)

            (Macsai 2008) Download

PURPOSE: Blepharitis and meibomian gland dysfunction (MGD) are common sources of complaints from patients. To evaluate the effect on ocular symptoms, ocular findings, and serum and meibomian gland contents, patients with blepharitis and MGD were prospectively evaluated to determine the effects of dietary supplementation with omega-3 fatty acids. METHODS: In a prospective randomized placebo-controlled masked trial, patients with simple obstructive MGD and blepharitis, who had discontinued all topical medications and tetracyclines, received oral omega-3 dietary supplementation consisting of two 1000-mg capsules 3 times a day. Patients were examined every 3 months for 1 year with the Ocular Surface Disease Index (OSDI) objective clinical measures, including tear production and stability, ocular surface and meibomian gland health, and biochemical plasma, red blood cell (RBC), and meibum evaluation. Primary outcome measures were change in tear breakup time (TBUT), meibum score, and overall OSDI score at 1 year. RESULTS: At 1 year, the omega-3 group had a 36% and 31% reduction in their omega-6 to omega-3 fatty acid ratios in RBCs and plasma, respectively (P = .3), whereas the placebo group demonstrated no change. At 12 months, the omega-3 group had an improvement in TBUT, OSDI score, and meibum score. Changes in meibum content were observed in the omega-3 group (P = .21); the level of meibum saturated fatty acids decreased. CONCLUSIONS: This trial demonstrated a decrease in the RBC and plasma ratios of omega-6 to omega-3 in patients taking omega-3 dietary supplementation, as compared to controls, and improvements in their overall OSDI score, TBUT, and meibum score. This is the first demonstration of an induced change in the fatty acid saturation content in meibum as a result of dietary supplementation with omega-3 fatty acids.

Nutritional supplements for dry eye syndrome

         (Rand and Asbell 2011) Download

PURPOSE OF REVIEW: Essential fatty acids have been of interest in the treatment of systemic and ocular diseases, and is most recently of interest in the area of dry eye disease. RECENT FINDINGS: Systemic and topical omega-3 fatty acids and omega-6 fatty acids have been used recently as an adjunctive treatment for patients with dry eye disease. They appear to have efficacy against the symptoms of dry eye that many patients experience. This symptom is postulated to be secondary to the anti-inflammatory effects that have been previously described. Although this effect is promising, more investigation is warranted in order to standardize indication for use, and composition and dosing for treatment. SUMMARY: The use of essential fatty acids as a nutritional supplement is a novel treatment for patients with dry eye syndrome.

Androgen control of gene expression in the mouse meibomian gland

         (Schirra, Suzuki et al. 2005) Download

PURPOSE: In prior work, it has been found that the meibomian gland is an androgen target organ, that androgens modulate lipid production within this tissue, and that androgen deficiency is associated with glandular dysfunction and evaporative dry eye. This study's purpose was to test the hypothesis that the androgen control of the meibomian gland involves the regulation of gene expression. METHODS: Meibomian glands were obtained from orchiectomized mice that were treated with placebo or testosterone for 14 days. Tissues were processed for the analysis of differentially expressed mRNAs by using gene bioarrays, gene chips, and real-time PCR procedures. Bioarray data were analyzed with GeneSifter software (VizX Labs LLC, Seattle, WA). RESULTS: The results show that testosterone influenced the expression of more than 1590 genes in the mouse meibomian gland. This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin B), and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A). Some of the most significant androgen effects were directed toward stimulation of genes associated with lipid metabolism, sterol biosynthesis, fatty acid metabolism, protein transport, oxidoreductase activity, and peroxisomes. CONCLUSIONS: These findings demonstrate that testosterone regulates the expression of numerous genes in the mouse meibomian gland and that many of these genes are involved in lipid metabolic pathways.


Identification of steroidogenic enzyme mRNAs in the human lacrimal gland, meibomian gland, cornea, and conjunctiva

            (Schirra, Suzuki et al. 2006) Download

PURPOSE: Sex steroids exert a significant influence on the health and well-being of the ocular surface and adnexa. These hormones affect multiple aspects of the lacrimal and meibomian glands, conjunctiva, and cornea, and have been linked to the development of many ocular surface pathologies. We hypothesize that these hormone actions, as in other tissues, occur predominantly after the local synthesis of androgens and estrogens from adrenal precursors. To begin to test this hypothesis, we analyzed whether human ocular surface and adnexal tissues and cells contain the steroidogenic enzyme mRNAs necessary for the intracrine synthesis and metabolism of sex steroids. METHODS: Total RNA was isolated from human lacrimal and meibomian glands and immortalized corneal and conjunctival epithelial cells. Samples were reverse transcribed to cDNA and analyzed for the presence of enzyme mRNAs by real-time PCR. Positive and negative controls included human placental cDNA and the absence of template, respectively. RESULTS: Our results show that human lacrimal and meibomian glands and corneal and conjunctival epithelial cells contain the mRNAs for steroid sulfatase, 3beta-hydroxysteroid dehydrogenase (HSD)-Delta-Delta-isomerase type 1, 17beta-HSD types 1 and 3, aromatase, and glucuronosyltransferase. In contrast, only lacrimal and meibomian tissues appeared to contain detectable mRNA for sulfotransferase. CONCLUSIONS: If the corresponding mRNAs are translated, our results indicate that human ocular surface and adnexal tissues contain the enzymatic machinery necessary for the intracrine synthesis and metabolism of sex steroids.

Combined esterified estrogen and methyltestosterone treatment for dry eye syndrome in postmenopausal women

         (Scott, Yiu et al. 2005) Download

PURPOSE: To determine whether systemic replacement with combined esterified estrogen (EE) and methyltestosterone (MT) (EE + MT) would reduce symptoms and promote clinical improvement in postmenopausal women with dry eye syndrome (DES). DESIGN: Retrospective, noncomparative, interventional case series. METHODS: Investigators reviewed the charts of 11 postmenopausal women treated within the last 3 years with EE + MT. RESULTS: The mean patient age was 65.2 years (standard deviation [SD] 11.4, range 48-84 years). The mean treatment duration was 12.2 months (SD 6.2 months, range 4-24 months). Ten (91%) of 11 patients reported improvement in dry eye symptoms while receiving treatment. For these 10, relief occurred after an average of 4.1 months of treatment (SD 3.2, range, 1-9 months). CONCLUSIONS: Treatment with EE + MT may be efficacious for DES of various etiologies. A randomized placebo-controlled trial is planned to further evaluate these encouraging findings.


Androgen influence on the meibomian gland

         (Sullivan, Sullivan et al. 2000) Download

PURPOSE: The hypothesis in the study was that androgens control meibomian gland function, regulate the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer. To test this hypothesis, a study was conducted to determine whether androgen receptor protein exists in the epithelial cell nuclei of rat meibomian glands and, in addition, whether androgen deficiency and/or treatment influences the gross morphology, neutral lipid content, and fatty acid profile of the rabbit meibomian gland, as well as the appearance of the tear film lipid layer. METHODS: Rat lids were obtained and processed for immunohistochemistry. Meibomian glands from intact, androgen- and/or placebo-treated rabbits were analyzed by histology, and glandular lipids were evaluated by gas chromatography, high-performance liquid chromatography (HPLC), and mass spectrometry. The rabbit tear film lipid layer was assessed by interferometry. RESULTS: In the current study androgen receptor protein existed within acinar epithelial cell nuclei of rat meibomian glands; androgen deficiency was associated with alterations in the lipid content of the rabbit meibomian gland; 19-nortestosterone treatment modulated the fatty acid profile in the total and neutral lipid fractions of the rabbit meibomian gland; and androgens did not appear to influence the gross morphology of meibomian tissue or to exert a demonstrable effect on the rabbit tear film lipid layer. CONCLUSIONS: The findings show that the meibomian gland is an androgen target organ and that androgens influence the lipid profile within this tissue. However, the extent to which androgens regulate the production of these lipids and whether this action may impact tear film stability remain to be determined.

Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye

            (Sullivan, Sullivan et al. 2002) Download

OBJECTIVE: We have recently discovered that women with primary and secondary Sjogren'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 Sjogren'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 Sjogren's syndrome.

Complete androgen insensitivity syndrome: effect on human meibomian gland secretions

            (Sullivan, Evans et al. 2002) Download

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.


Sex steroids, meibomian gland dysfunction and evaporative dry eye in Sjogren's syndrome

            (Sullivan, Schaumberg et al. 2002) Download

Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands?

            (Sullivan, Jensen et al. 2009) Download

PURPOSE: We hypothesize that sex steroids induce sex-specific and/or opposite effects in the lacrimal and meibomian glands and that these actions may influence the prevalence of dry eye syndrome. The objective of this study was to begin to test this hypothesis. METHODS: Lacrimal and meibomian glands were obtained from ovariectomized mice that had been treated with testosterone or control vehicle for 14 days. Samples were processed for the isolation of RNA, and analyzed for differentially expressed mRNAs using CodeLink Bioarrays and quantitative real-time PCR (qPCR) techniques. Data were compared to those obtained following testosterone treatment of orchiectomized mice, as well as after the administration of 17beta-estradiol and/or progesterone to ovariectomized mice. RESULTS: Our findings demonstrate that testosterone regulates the expression of thousands of genes in the lacrimal and meibomian glands of ovariectomized mice. The magnitude and extent of these hormonal effects, which encompassed numerous biological, molecular, and cellular ontologies, was tissue-dependent. Particularly notable was the androgen stimulation of meibomian gland genes related to lipid metabolic pathways, and the suppression of genes associated with keratinization. Many of the genes regulated by testosterone in female tissues were identical to those controlled by androgens in male lacrimal and meibomian glands. However, some genes were modulated in a sex-specific manner. In addition, a number of the androgen-regulated genes in female glands were altered in the opposite direction by 17beta-estradiol and/or progesterone. CONCLUSIONS: Our results support our hypothesis that sex steroids may induce sex-specific and/or opposite effects in the lacrimal and meibomian glands. Whether these actions contribute to the prevalence of dry eye remains to be determined.

Do estrogen and progesterone play a role in the dry eye of Sjogren's syndrome?

            (Suzuki, Schaumberg et al. 2002) Download


Estrogen and progesterone control of gene expression in the mouse meibomian gland

            (Suzuki, Schirra et al. 2008) Download

PURPOSE: The purpose of the study was to test the hypothesis that estrogen and progesterone regulate gene expression in the meibomian gland. METHODS: Meibomian glands were obtained from young adult, ovariectomized mice that were administered 17beta-estradiol, progesterone, 17beta-estradiol plus progesterone, or vehicle for 14 days. Glands were pooled according to treatment, processed for the extraction of RNA, and analyzed for differentially expressed mRNAs by using mouse gene microarrays. Bioarray data were evaluated with sophisticated bioinformatics software and statistical programs. The expression of selected genes was confirmed with gene chips and quantitative real-time PCR techniques. RESULTS: The findings show that 17beta-estradiol, progesterone, or both hormones administered together significantly influenced the expression of numerous genes in the mouse meibomian gland. Notable were the effects of 17beta-estradiol on genes related to lipid metabolism, tyrosine kinases, immune factors, extracellular matrix components, steroidogenesis, and prolactin dynamics. Also very significant were the actions of progesterone or 17beta-estradiol plus progesterone on ribosome or localization gene ontologies, respectively. The various hormone treatments led to many analogous, opposite, or unique effects on gene expression. CONCLUSIONS: These findings support the study hypothesis that estrogen and progesterone modulate gene expression in the meibomian gland.

Testosterone-induced suppression of autoimmune disease in lacrimal tissue of a mouse model (NZB/NZW F1) of Sjogren's syndrome

            (Vendramini, Soo et al. 1991) Download

The current investigation was designed to examine whether androgen administration might suppress autoimmune disease in lacrimal glands of a mouse model (NZB/NZW F1) of Sjogren's syndrome. Autoimmune, female mice were treated with vehicle or varying concentrations of testosterone for 0, 17, 34, or 51 days, and tears, lacrimal glands, as well as submandibular tissue, were collected from killed mice after androgen exposure. Glands were histologically processed and evaluated with a computer-assisted image analysis system. Results showed that testosterone administration induced a significant, time-dependent decrease in the extent of lymphocytic accumulation in the lacrimal gland. After 34-51 days of androgen therapy, the magnitude of lymphocyte infiltration had been suppressed 22- to 46-fold, compared with that in placebo-treated tissue. This hormone effect was associated with significant reductions in the number of focal infiltrates, the area of individual foci, and the total quantity of lymphocyte infiltration per lacrimal section. Testosterone exposure also stimulated an increase in lacrimal gland weight and a rise in tear volumes, relative to those measured in the same mice before treatment. In addition, androgens significantly diminished the extent of lymphocyte accumulation in submandibular tissue. In summary, our results demonstrate that androgen administration may inhibit the progression of autoimmune disease in lacrimal and submandibular glands of NZB/NZW F1 mice.


References

Duarte, M. C., N. T. Pinto, et al. (2007). "[Total testosterone level in postmenopausal women with dry eye]." Arq Bras Oftalmol 70(3): 465-9.

Erdem, U., O. Ozdegirmenci, et al. (2007). "Dry eye in post-menopausal women using hormone replacement therapy." Maturitas 56(3): 257-62.

Goto, E., J. Shimazaki, et al. (2002). "Low-concentration homogenized castor oil eye drops for noninflamed obstructive meibomian gland dysfunction." Ophthalmology 109(11): 2030-5.

Khandelwal, P., S. Liu, et al. (2012). "Androgen regulation of gene expression in human meibomian gland and conjunctival epithelial cells." Mol Vis 18: 1055-67.

Knop, E., N. Knop, et al. (2011). "The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland." Invest Ophthalmol Vis Sci 52(4): 1938-78.

Krenzer, K. L., M. R. Dana, et al. (2000). "Effect of androgen deficiency on the human meibomian gland and ocular surface." J Clin Endocrinol Metab 85(12): 4874-82.

Macsai, M. S. (2008). "The role of omega-3 dietary supplementation in blepharitis and meibomian gland dysfunction (an AOS thesis)." Trans Am Ophthalmol Soc 106: 336-56.

Rand, A. L. and P. A. Asbell (2011). "Nutritional supplements for dry eye syndrome." Curr Opin Ophthalmol 22(4): 279-82.

Schirra, F., T. Suzuki, et al. (2006). "Identification of steroidogenic enzyme mRNAs in the human lacrimal gland, meibomian gland, cornea, and conjunctiva." Cornea 25(4): 438-42.

Schirra, F., T. Suzuki, et al. (2005). "Androgen control of gene expression in the mouse meibomian gland." Invest Ophthalmol Vis Sci 46(10): 3666-75.

Scott, G., S. C. Yiu, et al. (2005). "Combined esterified estrogen and methyltestosterone treatment for dry eye syndrome in postmenopausal women." Am J Ophthalmol 139(6): 1109-10.

Sullivan, B. D., J. E. Evans, et al. (2002). "Complete androgen insensitivity syndrome: effect on human meibomian gland secretions." Arch Ophthalmol 120(12): 1689-99.

Sullivan, D. A., R. V. Jensen, et al. (2009). "Do sex steroids exert sex-specific and/or opposite effects on gene expression in lacrimal and meibomian glands?" Mol Vis 15: 1553-72.

Sullivan, D. A., D. A. Schaumberg, et al. (2002). "Sex steroids, meibomian gland dysfunction and evaporative dry eye in Sjogren's syndrome." Lupus 11(10): 667.

Sullivan, D. A., B. D. Sullivan, et al. (2002). "Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye." Ann N Y Acad Sci 966: 211-22.

Sullivan, D. A., B. D. Sullivan, et al. (2000). "Androgen influence on the meibomian gland." Invest Ophthalmol Vis Sci 41(12): 3732-42.

Suzuki, T., D. A. Schaumberg, et al. (2002). "Do estrogen and progesterone play a role in the dry eye of Sjogren's syndrome?" Ann N Y Acad Sci 966: 223-5.

Suzuki, T., F. Schirra, et al. (2008). "Estrogen and progesterone control of gene expression in the mouse meibomian gland." Invest Ophthalmol Vis Sci 49(5): 1797-808.

Vendramini, A. C., C. Soo, et al. (1991). "Testosterone-induced suppression of autoimmune disease in lacrimal tissue of a mouse model (NZB/NZW F1) of Sjogren's syndrome." Invest Ophthalmol Vis Sci 32(11): 3002-6.