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Indian Journal of Ophthalmology logoLink to Indian Journal of Ophthalmology
. 2023 Apr 5;71(4):1276–1284. doi: 10.4103/IJO.IJO_2887_22

Hormones and dry eye disease

Bhavya Gorimanipalli 1, Pooja Khamar 1, Swaminathan Sethu 1, Rohit Shetty 1,
PMCID: PMC10276676  PMID: 37026259

Abstract

The endocrine system influences all tissues and cells in the human body. The ocular surface is constantly exposed to circulating hormones and expresses their specific receptors. Dry eye disease (DED) is a disorder with multifactorial etiology, and endocrine anomalies are one of the inciting factors. The endocrine anomalies that cause DED include physiological conditions such as menopause, menstrual cycle variations, pathologies such as polycystic ovarian syndrome, androgen resistance, iatrogenic conditions such as contraceptive use, and antiandrogen treatment. This review highlights the status of these hormones in DED along with the mechanism of action of different hormones on the ocular surface structures and the clinical implications of these effects. The influence of androgens, estrogens, and progesterone on the ocular surface tissues, and the implications of androgen-deficient states in DED are also discussed. The physiological and pathological effects of menopause and sex hormone replacement therapy are discussed. The effects of insulin and insulin resistance on the ocular surface and DED, and the growing potential of topical insulin therapeutics for DED are mentioned. Thyroid-associated ophthalmopathy, its impact on the ocular surface, and the tissue effects of thyroid hormone in the context of DED are reviewed. Finally, the potential role of hormonal therapeutics in the management of DED has also been discussed. The compelling evidence suggests that it would be clinically beneficial to consider the possibility of hormonal imbalances and their impact while treating patients with DED.

Keywords: Dry eye disease, hormones, inflammation, menstrual cycle, ocular surface, tear fluid


A variety of physiological and environmental conditions lead to the development of dry eye disease (DED).[1] Even though an increase in osmolarity and ocular surface inflammation is its cardinal features, DED is a multifactorial disease. Among many other factors, endocrine abnormalities are significant contributors to DED.[2,3] The endocrine system is an integral organ system that controls various physiological responses and interactions with our environment. Like any other organ, the ocular surface is influenced by many circulating hormones and is under constant feedback control by these mediators. This review discusses the mechanisms and clinical relevance of endocrine system effects on the ocular surface and DED that may have a direct impact on the clinical management of DED.

The ocular surface comprises of interconnected tissues with epithelial continuity. It consists of the cornea, conjunctiva, lacrimal gland, accessory lacrimal glands, meibomian gland, eyelashes, the glands located near lashes (glands of Moll and Zeis), eyelid components involved in the blinking reflex, and nasolacrimal duct.[4] All of these structures share integrated vascular, nervous, and endocrine inputs.[4] They have a continuous epithelial layer spreading across the surfaces of the cornea, conjunctiva, glandular structures, and the nasolacrimal duct. This epithelial layer has a single developmental origin, which is the surface ectoderm. The ocular surface works as a single functional unit, with the purpose of enabling a smooth surface for optimal functioning of the cornea as a refractive interface. Several hormones including sex steroids, thyroid hormone (TH), vitamin D, prolactin, growth hormone, and many others play a critical role in supporting the morphology and function of the ocular surface.

Sex as a Biological Variable in Ocular Surface Physiology and DED

Sex or gender diversity is a critical variable influencing every single biological function in the living world. Ocular surface physiology is no different in this case. It is apparent that considering sex as a biological variable is essential to deliver personalized care.[5] In the next few sections, we will discuss the unique effects of sex hormones on the ocular surface structures. It is an established fact that women suffer more frequently from DED than men.[6] The self-reported symptoms of DED were more severe, and frequent, and had a higher impact on well-being among women than that in men.[6] There are two types of population-based surveys that focus on DED.[7-9] Few surveys assessed the prevalence of DED in female cohorts, while others compared the prevalence of DED between men and women in the general population. Women’s Health Study, a large health survey conducted in North America, reported a staggering 9.5% prevalence of DED in women aged more than 75 years.[7] The same study group (Schaumberg et al.) assessed the prevalence of DED in men with a similar methodology and reported a 70% higher prevalence of DED among women compared to men in the 50 years and older age group.[8] Among 1174 Australian participants, who underwent dry eye examination and completed a dry eye questionnaire, dry eye symptoms were reported to be more frequent in women.[9] It is interesting that women report more discomfort from ocular surface conditions like pterygium than men with a similar condition.[10] Sjogren’s syndrome is an aqueous deficient DED condition, with underlying autoimmune etiology. Androgen deficiency is suggested to be an etiological factor in the pathogenesis of Sjogren’s syndrome.[11] Sex-associated changes increase in the expression of mediators that reduce inflammation in salivary glands was demonstrated in Sjogren’s syndrome animal models.[12] Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder among women characterized by ovarian dysfunction (oligo-ovulation and polycystic ovaries) and features of hyperandrogenism.[13] Women with PCOS were shown to have more severe DED symptoms, lower Schirmer test scores, and TBUT values compared to healthy women.[14] The distinctive ocular surface morphology in women with PCOS has been described as itchy-dry eye-associated syndrome (IDEA) by Bonini et al.[3] The authors reported that the ocular surface disease in these patients shared many features with dry eye disease and allergic eye disease but has a concomitant endocrine disorder.[3] Altered sex steroids and insulin resistance play a critical role in causing ocular surface disturbances in these patients.[15] Higher levels of sex steroids are shown to inhibit insulin binding sites and lower the action of insulin on the ocular surface.[16]

Androgens

Androgens exert a trophic effect on the meibomian gland’s growth and function.[17] Meibomian gland expresses mRNAs of enzymes responsible for the metabolism of testosterone to its more potent metabolite, dihydrotestosterone (DHT).[18] It has been shown that the mouse meibomian gland expresses androgen-regulated genes, which depending on the stimulation of androgen receptors, are responsible for gender-specific expression in the tissue.[19] Androgens stimulate the genes involved in the production, transport, and secretion of lipids in the meibomian gland.[20-22] Androgen deficiency has detrimental effects on meibomian gland morphology and function.[23-25] Antiandrogen treatment is shown to adversely affect the lipid profile of the meibomian gland secretions.[26] Similarly, women with androgen insensitivity syndrome and men on antiandrogen treatment are shown to have increased tear film debris, irregular posterior lid margins, tarsal conjunctival congestion, meibomian gland orifice metaplasia, and a significant decrease in the tear break-up time.[25] Furthermore, androgen deficiency has been pointed out as an important etiological factor in the pathogenesis of evaporative dry eye in women with Sjogren’s syndrome.[27]

The lacrimal gland is a bilobed exocrine gland with the primary function of secreting water, proteins, and electrolytes which contribute to the aqueous layer of the tear film. Testosterone regulates the expression of several genes in the lacrimal gland including those involved in cell growth, proliferation, metabolism, cell communication and transport, nucleic acid binding, signal transduction, and receptor activities.[19] Lacrimal gland acinar cells express high-affinity androgen-specific receptors and the said effects on the gene expression in lacrimal glands, could be mediated through these receptors.[28] This influence of androgens on lacrimal glands contributes to many of the sex-related differences in gene expression of the lacrimal gland. Testosterone provides trophic support to lacrimal glands and increases lacrimal glands’ tissue growth and activity. Chronic exposure to androgen receptor antagonists results in degenerative changes in lacrimal glands like loss of glandular elements, reduction in acinar cell size, reduction in nuclear volume, changes in protein levels, and changes in enzymatic activity.[29] Testosterone favorably influences the ocular surface and lacrimal glands’ immune functions. In a study by Sullivan and Hann,[30] androgens were demonstrated to increase the lacrimal gland production and secretion of IgA. Due to the pleiotropic effect of androgen on the ocular surface [Fig. 1], its alteration contributes towards DED.

Figure 1.

Figure 1

Ocular surface effects of androgens, estrogen, and progesterone. Schematic outlines the various key ocular surface cellular events regulated by sex hormones that may have an influence on the different factors that contribute to the pathogenesis of dry eye disease

Estrogens and Progesterone

Estrogen and progesterone receptors are present in various ocular surface structures including the cornea, conjunctiva, meibomian gland, and lacrimal gland, and many ocular surface structures.[31,32] Hence, it can regulate key cellular events on the ocular surface [Fig. 1]. Estrogens appear to have antagonizing effects on the physiology of the meibomian gland compared to androgens. In animal studies, 17ß-estradiol stimulated the genes involved in lipid and fatty acid catabolism and downregulated the genes involved in lipid synthesis.[33] Injection of estrogens induced shrinkage, reduction in activity, and lipid synthesis of sebaceous glands in humans and many other species.[34-37] These limiting effects of estrogens on the physiology of the meibomian gland can help explain the worsening of dry eye symptoms and signs in postmenopausal women on sex hormone replacement therapy (SHRT).[38-40] However, the same would not explain the increased prevalence of DED in postmenopausal women who were not on any form of SHRT.[7,41] This aging population also has reduced levels of androgens similar to their male counterparts. The loss of trophic support of androgens on the meibomian gland is more critical to the worsening of tear film instability and other DED signs in aged women than the reduced estrogen support.[42]

The nature of the influence of estrogens on the lacrimal gland is more controversial than that of androgens. Few studies suggest that estrogen may play a minimal role in the anatomy and physiology of the lacrimal gland.[43] But others demonstrated that estrogens have an adverse influence on the lacrimal gland, such as inducing glandular regression, acinar cell disruption, and necrosis.[44] There are other groups of reports supporting the positive influence of estrogens on the lacrimal gland. The reduction in lacrimal gland function in postmenopausal women with estrogen deficiency may support this theory.[45] The effect of estrogen replacement on the lacrimal gland is controversial as well. Few reports show restoration of lacrimal gland morphology and activity,[46,47] while a number of studies show worsening of lacrimal gland function and dry eye with estrogen replacement therapy.[38]

Intracrine effects of sex hormones on the ocular surface

It is intriguing to note that the ocular surface including the lacrimal gland is capable of local synthesis of sex steroids from their precursors.[48] The term “intracrinology” refers to this local synthesis of hormones in the peripheral tissues from their circulating precursors.[48] The majority of androgens in women and a significant proportion in men are locally synthesized in peripheral tissues from dehydroepiandrosterone (DHEA) and DHEA-sulfate, the precursors, secreted by the adrenal gland.[49,50] The synthesis of sex hormones in peripheral tissues helps them adjust the formation and metabolism of these hormones to local requirements. The intracrine metabolism of sex hormones paved way for experimental use of topical therapeutic formulations of DHEA in the form 1% DHEA drops in the management of DED.[51]

Effects of menstrual cycle and menopause on the ocular surface and DED

The ocular surface shows cyclical changes in its structure and function that mirror the cyclical variations in the circulating estrogen and progesterone hormone levels. The maturation index of conjunctival epithelium shows cyclical variations in women in the reproductive age group, suggesting that conjunctival epithelium is an estrogen-receptive epithelium.[52] The cornea shows variations in thickness, biomechanical strength, and sensitivity during different phases of the menstrual cycle. The cornea is thinnest at the beginning of the cycle and becomes thicker toward the end of the cycle.[53,54] The corneal sensitivity showed a reduction during the ovulation phase.[55] The trend in ocular symptoms is more variable, some studies suggested worsening of symptoms during ovulation,[56] while others showed more severe symptoms during the follicular phase.[57] Few reports suggested no demonstrable changes in the ocular surface parameters along the menstrual cycle.[58]

Estrogens were suggested to upregulate pro-inflammatory cytokines including MMP9 in human corneal epithelial cells.[59] There are reports that were suggestive of the anti-inflammatory effects of estrogen on the ocular surface and other organs in the human body, as well.[60-62] Systemic estrogen concentrations undergo cyclical changes in premenopausal women. Evidence suggests the cytokine milieu of the estrogen-responsive tissues, changes during different phases of the menstrual cycle mirroring the variations in estrogen levels.[63,64] Since the ocular surface expresses estrogen receptors and is responsive to this hormone, its cytokine milieu is expected to show variations during the menstrual cycle. We investigated the status of tear fluid concentrations of various inflammatory cytokines at three different phases of the menstrual cycle in healthy female subjects. We observed eye or subject-specific alteration in the levels of the inflammatory cytokines in the tear fluid in the ovulation phase and luteal phase compared to the early follicular phase. More specifically, the tear fluid levels of IL-1β, IL-6, and VEGF were observed to be increased in a greater number of eyes or subjects in the ovulation and luteal phase compared to the early follicular phase [Fig. 2]. It is interesting to note that though statistically insignificant, 50% of the eyes or subjects showed an increase in the MMP9 levels in the ovulation and luteal phase compared to the early follicular phase [Fig. 2]. This change in the tear inflammatory cytokines can potentially impact the severity of DED, corneal wound healing, and many other ocular surface functions that are modulated by these cytokines. These findings emphasize the relevance of the menstrual cycle during disease monitoring and/or treatment planning.

Figure 2.

Figure 2

Alterations in tear fluid inflammatory cytokines during different menstrual cycle phases in healthy female subjects. The stacked bar graphs indicate the proportion (percentage) of eyes that showed changes (increased by ≥1.2 fold or decreased by ≤1.2 fold) in the tear cytokine levels in matched samples between the three phases of the menstrual cycle. Tear fluid collected using Schirmer strips in the three different phases (Phase 1—Early follicular phase; Phase 2—Ovulation phase; Phase 3—Luteal phase) was used to measure the levels of interleukin (IL)-1β, IL-10, IL-6, IL-17A, tumor necrosis factor-α (TNFα), matrix metalloproteinase 9 (MMP9), soluble intercellular adhesion molecule 1 (sICAM1), and vascular endothelial growth factor-A (VEGF-A) using a microfluidic cartridge-based multiplex ELISA kit (Bio-M Pathfinder, NovoMol-Dx, India, a customized version of the Ella™ Automated ELISA system, Bio-Techne® Corporation, Minnesota, USA). The menstrual cycle phases were calculated based on the average duration of the menstrual cycle and the timing of the last menstrual period in healthy women (n = 15; 30 eyes) aged between 25 and 35 years with regular menstrual cycles. The samples were collected following institutional ethics committee approval and informed consent of the study volunteers. The levels of IL-17A, TNFα, and sICAM1 did not vary significantly and did not show a marked increase in the proportion of eyes with increased levels of these factors between three phases of the menstrual cycle in the matched tear samples

Menopause is a physiological change not just the endocrine system but the entire human body itself. There are three pertinent changes in a systemic endocrine milieu that should be kept in mind when we try to understand the concept of DED in postmenopausal women. There is aging-associated decrease in androgen levels in these women,[65] along with a reduction in circulating estrogen levels and possible reduction in the ocular surface synthesis of estrogen from its precursors (intracrine pathways). As mentioned earlier, DED is more prevalent in postmenopausal women compared to men of similar age. Endogenous estrogen levels are critical in the maintenance of ocular surface homeostasis in postmenopausal women. But the existing reports showed conflicting results, few authors suggested low estradiol levels correlated with severe dry eye,[66] while others suggested higher concentrations of estradiol were predictive of worse meibomian quality.[67]

Effect of estrogen and progesterone replacement therapy in DED

The clinical effects of estrogen and progesterone replacement therapy in women are complex and depend on the age, pre-treatment sex hormone levels, ovarian physiology, and the mode of treatment. Health surveys with large sample cohorts and smaller clinical studies demonstrated that SHRT in postmenopausal women increased the prevalence of DED.[38,68] However, few reports suggest the beneficial role of SHRT on tear secretion and stability and DED symptoms.[69,70] The type of hormonal constituents may impact the clinical effects of SHRT. The estrogen replacement alone may cause dry eye more frequently than combined estrogen and progesterone therapy.[38,68]

Thyroid Hormone

In this section, we discuss the ocular surface effects of dysthyroid and autoimmune thyroid disorders in the development of DED [Fig. 3]. The terms thyroid eye disease (TED), thyroid-associated ophthalmopathy (TAO), thyroid-associated orbitopathy (TAO), and Grave’s ophthalmopathy indicate an immune-mediated inflammatory disease condition that causes expansion of the extraocular muscles and fat in the orbit. Tear film and ocular surface changes are prevalent in patients with thyroid-associated ophthalmopathy (TAO).[2,71] Patients with active TED showed signs of severe meibomian gland dysfunction (MGD).[72] Studies using meibography in patients with active TED showed increased structural loss of the meibomian gland compared to patients with DED.[73,74] Kim et al. reported a higher prevalence of obstructive MGD in patients with Graves orbitopathy compared to normals.[75] DED in patients with TAO occurs due to two main reasons. First, an increase in the palpebral fissure width and poor Bell’s phenomenon in these patients leads to accelerated tear evaporation, increases the tear osmolarity, and results in ocular surface damage.[2,71] These patients show low TBUT scores, and high ocular surface staining scores (rose bengal and lissamine green) indicating unhealthy ocular surface. Second, the lacrimal gland inflammation is due to autoimmune mechanisms directed at the thyroid stimulating hormone (TSH) receptors expressed by the LG. Lacrimal gland enlargement in TAO has been reported as early as 1981[76] and many radiological studies confirmed this observation.[77-79] The gland enlargement is due to active lymphocytic infiltration and interstitial edema during the disease process.[76,80] Lacrimal gland tissue expresses receptors for the TSH similar to thyroid epithelial cells. TSH receptor (TSHR) is an established auto-antigen for TAO disease. TSHR expression makes lacrimal gland tissue susceptible to autoimmunity-induced inflammation and damage in patients with TAO.[81] Reduction in tear secretion and the increased tear fluid inflammatory cytokines further suggest that the lacrimal gland is affected by the inflammatory process of TAO.[81]

Figure 3.

Figure 3

Dry eye disease mechanisms in thyroid disorders. Schematic illustrates the pathomechanisms underlying ocular surface changes in thyroid-associated orbitopathy that may contribute toward the development of dry eye disease. TSHR—Thyroid stimulating hormone receptor

Hashimoto’s thyroiditis is also an autoimmune disorder with hypothyroidism. Lacrimal gland inflammation may not be the only pathogenic mechanism behind DED in patients with autoimmune thyroid disorders. Lacrimal gland acinar epithelial cells, conjunctival and corneal epithelial cells express thyroid hormone receptor ß-1 (Thrb), and nuclear receptor for thyroid hormone (TH).[82] Dias et al. showed that chronic hypothyroidism resulted in reduced tear secretion and induced Thrb upregulation in lacrimal gland tissue (interpreted as a compensatory response).[82] These observations show that in addition to autoimmune damage, lower TH stimulation of the lacrimal gland could be the possible etiopathogenetic factor behind DED in patients with TAO.

It is essential to suspect and identify occult TED in patients with DED. In a clinical study by Gupta et al., 21/539 patients with DED had occult thyroid eye disease (TED).[83] Conjunctival hyperemia with or without chemosis localized to extraocular muscles and subtle widening of interpalpebral fissures were reported as the clinical signs that made the treating physician suspect TED in these patients.[83] The treatment aimed at TAO can destabilize the ocular surface in these patients. Orbital radiotherapy to treat TAO has been shown to cause DED.[84-86] Furthermore, surgical interventions aimed to correct lid retraction in TAO may inadvertently injure the lacrimal gland.[87] To effectively manage DED in patients with TAO, one should aim to treat exposure keratopathy (lubricants, particularly overnight), to reduce tear osmolarity (artificial tears, therapies to reduce surface osmotic damage),[88] and to reduce ocular surface inflammation (topical steroids, topical cyclosporine A).[89]

Vitamin D

Vitamin D (VD) is considered as a prohormone and was initially known to be the compound found in cod liver oil, that treats rickets. Since it is a compound present in food and is essential for the mineralization of bone, VD was considered as a vitamin.[90] However, after the discovery of the role of ultraviolet rays in the metabolism of VD, and its involvement in the physiology of tissues other than the maintenance of calcium homeostasis in the skeleton. It is implicated in local and systemic immune regulation, tissue differentiation, and apoptosis.[91] VD binds to the VD receptor (VDR), a nuclear receptor, which further binds to the vitamin D response elements (VDRE) in the target genes as a heterodimer with retinoid X receptor.[92] The levels of ocular surface VD and VDR have been reported to be reduced in DED patients.[93,94] VD improves ocular surface epithelial barrier function,[95] reduces ocular surface inflammation,[96] improves tear osmolarity,[97] and alleviates the hyperosmotic stress.[94] VD supplementation aids in the management of patients with refractory DED,[98] corneal neuralgia,[99] and improves the efficacy of artificial tear drops.[100]

Insulin

The cross talk and inter-regulation between insulin and hormone regulation are well known. Patients with insulin-dependent diabetes mellitus (IDDM) were shown to have significantly lower reflex tearing.[101] Children with DM had a higher prevalence of DED compared to those without DM.[102] DED was found to be more prevalent in diabetic patients with microvascular complications.[103] Apart from chronic hyperglycemia and increased oxidative stress, reduced insulin levels have a direct effect on the ocular surface tissues. Insulin improves the secretory function of the lacrimal gland.[104] Insulin has a synergistic action with androgens on lacrimal gland function.[105] Reduction in insulin levels diminished the effect of androgens on the acinar cultures and decrease cell maintenance.[104] Local hyperglycemia on the ocular surface and tear fluid causes the increased formation of advanced glycation end products (AGE) and oxidative stress-mediated tissue damage.[106] Glycemic control appears to play a critical role in DED severity. The serum levels of glycated hemoglobin (HbA1c) are shown to have a significant association with tear film stability and dry eye symptoms.[106] Topical ophthalmic insulin preparations were demonstrated to improve tear volume and corneal cell architecture.[107]

Glucocorticoids, Prolactin, Growth Hormone

Glucocorticoids (GCs) are intrinsic modulators of the inflammatory response in various tissues including the ocular surface. Human corneal epithelial cells and fibroblasts are capable of intracrine synthesis of cortisol (an endogenous active form of GCs) due to the presence of 11-beta hydroxysteroid dehydrogenases, enzymes that catalyze the conversion of cortisone to cortisol.[108] Cortisol provides support to ocular surface innate immune response and contributes to immune protection.[108] It is well known that the effect of cortisol in inflammation regulation is dualistic, i.e. it has both pro- and anti-inflammatory roles. It is dynamic and the nature of its effect on inflammation regulation is influenced by its concentration, diurnal changes, stress, and sex.[109] The anti-inflammatory effect of GCs on the ocular surface is sex influenced, and this may contribute to the sexual dimorphic nature of autoimmune disorders of the ocular surface.[110] Prolactin has been implicated for its pro-inflammatory effects and role in the pathogenesis of autoimmune diseases.[111,112] Patients with Sjogren’s syndrome had significantly higher serum prolactin levels than controls.[113] Similarly, a significant negative correlation was found between serum prolactin levels and tear function in women on SHRT.[114] Growth hormone (GH) appears to have a positive influence on the physiology of ocular surface structures like the meibomian gland.[115] However, no significant association was reported between clinical conditions involving anomalies of GH function and DED.

Hormone Preparations as Treatment for DED

Topical application of DHEA (precursor of testosterone) improves the TBUT through stimulatory and trophic effects on the production and secretion of lipids by the meibomian gland.[116] Topical androgen therapy in the form of testosterone eye drops is shown to improve tear film stability.[117,118] In contradiction to the clinical effects of systemic replacement, topical estrogen therapy improves dry eye symptoms, Schirmer test, and TBUT values.[119,120] Tibolone is a synthetic steroid with androgenic, estrogenic, and progestogenic properties. Several authors showed the effectiveness of tibolone in the treatment of Sjogren’s and non-Sjogren’s DED.[69,121] However, there is conflicting evidence on the clinical utility of this drug.[68] Low-dose hydrocortisone eye drops, either in combination with cyclosporine or trehalose, have been shown to be effective in the management of DED.[122-127] It is important to note that a very recent Cochrane review that evaluated the effectiveness of topical corticosteroids in DED management suggests that evidence is very low to moderate regarding its benefits, including its role on tear film quality.

Treatment for Endocrine Abnormalities and Its Effect on DED

Hormonal contraceptives (HC) do not appear to have any impact on tear physiology. Even though few reports suggested increased prevalence of DED in women using HC,[128,129] many other reports demonstrated no effect of HCs on the tear film metrics.[130-132] DED is an adverse effect of oral aromatase inhibitory therapy in women with breast cancer.[133-135] Aromatase catalyzes the conversion of androgens to estrogens in various tissues of the human body including the ocular surface.[133,134] The inhibition of aromatase possibly results in reduced systemic and local estrogen concentrations resulting in ocular surface dryness.[135]

Conclusion

Based on the aspects discussed in this article it is apparent that it is essential to consider the possibility of hormonal imbalances and their impact while treating patients with DED. Hormonal perturbation, either physiological (menopause, aging) or pathological (PCOS, TAO, DM), should be factored in during the diagnosis and treatment planning of DED. An informed and constructive collaboration between an ophthalmologist and an endocrinologist could help manage patients with DED, particularly those who are refractory to conventional treatment and with hormonal imbalances, more effectively.

Financial support and sponsorship

This work was supported by Narayana Nethralaya Foundation, Bangalore, India.

Conflicts of interest

There are no conflicts of interest.

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