At the completion of this article, the reader should be able to…
- Assess the limitations and potential risks of systemic hormone replacement therapy (HRT) in managing dry eye disease (DED) and understand the importance of interdisciplinary care.
- Understand the impact of menopause and fluctuating sex hormones on ocular surface health, particularly in relation to DED.
- Incorporate the B.E.I.S.T.O. protocol to systematically evaluate and manage the multifactorial drivers of ocular surface disease.
- Recognise the role of sex hormone receptors in ocular structures and their influence on tear film components, meibomian gland function, and inflammation.
Martin Robinson
BApp Sc(Optom)
Optometrist and principal owner, Martin’s Eyecare, Hobart
State president, Cornea and Contact Lens Society of Australia TAS (CCLSA)
National president, CCLSA
Dr Robin Abell
BMedSci, MBBS (Hons), MMed, FRANZCO
General ophthalmology, cataract, cornea and refractive surgeon, Hobart Eye Surgeons
Menopause is gaining recognition as a key driver of dry eye, with hormonal changes triggering inflammatory processes affecting the ocular surface. MARTIN ROBINSON and DR ROBIN ABELL explore ‘inflammopause’ and share practical strategies for supporting menopausal, perimenopausal and postmenopausal patients.
Menopause, defined as the permanent cessation of menstruation due to the age-related depletion of the ovarian follicle reserve, typically occurs between the ages of 45 and 55 and is diagnosed after 12 consecutive months of amenorrhea. It is preceded by the menopausal transition – commonly referred to as ‘perimenopause’ – a phase that can span several years (on average four to seven, but potentially up to 14 years).
Increasingly, the menopausal transitional phase is being recognised as ‘inflammopause’, highlighting the rise in systemic and local inflammatory processes driven by fluctuating hormone levels.
Ocular surface disease (OSD) is often attributed to general aging, but epidemiologic data consistently demonstrates significant sex-based differences, with women experiencing OSD at rates two to four times higher than men of the same age group.1 This disparity becomes even more pronounced following menopause, implicating hormonal decline as a contributing factor in the development and exacerbation of dry eye disease (DED).
Given that women can now spend more than half of their lives in a postmenopausal state, it is critical for eyecare professionals to recognise the broader ocular implications of oestrogen and progesterone deficiency. A foundational understanding of sex hormone physiology and its role in ocular surface health is essential to addressing the full spectrum of menopause-related eye conditions – beyond just dry eye.
Sex hormones and ocular surface
Sex hormones play a vital role in ocular surface health, exerting significant influence on corneal development, homeostasis, and disease through receptors found in key ocular structures. The ocular surface and its associated glands are hormone-
responsive, expressing functional receptors for androgens (AR), oestrogens (ERа and ERß), and progesterone (PR). These receptors are found throughout the cornea, conjunctiva (including goblet cells), lacrimal glands, and meibomian glands.
Their activity helps explain the growing recognition of sex hormones as important factors in the development and regulation of ocular surface disease (OSD).2
These receptors also have the capacity to synthesise endogenous sex hormones through localised enzymatic activity. 3 This suggests a more complex, tissue-specific hormonal microenvironment that may influence both ocular surface integrity and disease susceptibility.
The primary classes of sex hormones relevant to ocular function include androgens, such as testosterone; oestrogens; progestogens; and gonadotrophins, specifically follicle-stimulating hormone (FSH) and luteinising hormone (LH).4
Meibomian glands
Meibomian glands are crucial, producing lipid secretions essential for the tear film that prevent evaporation and maintain ocular surface integrity. Their lipid-producing cells, meibocytes, release meibum via holocrine secretion during blinking. Meibum’s complex composition is highly specialised; subtle alterations destabilise the tear film, driving ocular inflammation and dry eye symptoms.5,6
Androgens (e.g., testosterone), vital sex hormones in both genders, are now seen as protective against DED. While oestrogen decline was once the primary suspect, reduced androgen levels are now more directly linked to DED development and progression, particularly in women.5,7
Connecting hormonal shifts to ocular surface disruption and DED
Menopausal hormonal changes disrupt the lacrimal functional unit, causing tear film instability, hyperosmolarity, and ocular surface inflammation. Anatomical impacts include:
Aqueous
Hormones affect lacrimal glands, influencing the tear film’s aqueous component. Androgens support lacrimal gland function and may be anti-inflammatory; their age-related decline contributes to lacrimal gland inflammation and reduced aqueous production. Oestrogen’s role is complex: protective physiologically, but potentially pro-inflammatory or atrophic post-withdrawal or with HRT, leading to reduced tear secretion.8
Lipid
Hormones critically affect meibomian glands and thus the tear film’s lipid layer. Androgens are essential for meibomian gland function, stimulating lipid production and cell differentiation while suppressing ductal hyperkeratinisation. Androgen deficiency (from ageing, menopause, Sjögren’s, or anti-androgen therapies) is a key driver of meibomian gland dysfunction (MGD), causing ductal obstruction, altered meibum, gland atrophy, and tear film instability. Conversely, oestrogens may inhibit meibomian lipid production and promote keratinisation/atrophy, potentially explaining why oestrogen-containing HRT can worsen MGD.9
Stability
Hormonal influences also impact tear film stability. Deficient meibum increases tear evaporation, shortens tear break-up time (TBUT), and causes tear hyperosmolarity. This triggers ocular surface inflammation (cytokine/MMP release, immune cell recruitment). Resulting damage to epithelial and goblet cells reduces mucin, further destabilising the tear film in a self-perpetuating ‘vicious cycle’. Hormonal changes can exacerbate this by promoting inflammation and lowering the DED threshold.1,10
Role of Hormone Replacement Therapy
Systemic HRT’s relationship with DED is complex and not fully understood. Though oestrogen replacement was hypothesised to alleviate DED, large studies (e.g., Women’s Health Study) often show no benefit or even increased DED risk with systemic HRT, especially oestrogen-only formulations.11 Impact likely varies by hormone type, administration route, and individual factors.
Current recommendations for HRT and DED, include:
• Systemic HRT is for managing systemic menopausal symptoms (vasomotor, bone health, urogenital atrophy) based on a GP’s or specialist’s risk-benefit analysis.
• Systemic HRT is not currently a primary DED treatment.
• Optometrists should note HRT use in patient history, but not advise starting/stopping HRT for ocular reasons alone. GP collaboration is key if HRT status is relevant.
Research on topical ocular hormones (e.g., androgen/oestrogen eye drops) is ongoing, but not yet standard practice.
Diagnosing ocular issues in menopausal patients
As with all ocular surface and dry eye evaluations, start with a detailed case history and identify key drivers (modifiable and non-modifiable, medication and hormone related). The number of drivers of multifactorial DED can be overwhelming, which is why it is imperative to take a systematic approach, starting with a detailed case history as detailed in Table 1.
Patient responses inform triage and risk factor analysis. Plus, distinguishing modifiable factors requiring intervention from non-modifiable contributors need discussion. Diagnostic testing should follow.
A slit-lamp and fluorescein are fundamental for diagnosing DED. To determine an aqueous-
deficient subtype, Schirmer testing or tear meniscus assessment (via imaging) can be employed. Classification of evaporative DED is aided by slit-lamp examination combined with an eyelid push assessment. While meibography offers valuable insights, it is not essential, as modern diagnostic tools increasingly streamline the diagnostic process.
Identifying the DED subtype clarifies the underlying pathophysiology, enabling targeted treatment:
• Evaporative DED: Management focuses on lid and lash hygiene.
• Aqueous-deficient DED: Treatment involves tear supplementation and combination therapies.
The B.E.I.S.T.O. protocol
Managing OSD requires a tailored approach based on specific clinical findings. DED is multifactorial, and simply increasing lubricating drops or attributing symptoms solely to menopause is insufficient and outdated. Individualised care is especially important in patients with systemic conditions like Sjögren’s syndrome. Optometrists can use the B.E.I.S.T.O. protocol, developed by Dr Laura Periman, to guide a structured evaluation and inform targeted treatment. This framework helps identify and address key drivers of DED – bacteria, enzymatic dysfunction, inflammation, stasis, temperature sensitivity, and gland obstruction.
Each clinical sign should guide an appropriate intervention. For example, incomplete blinking may require blink training, lagophthalmos may benefit from sleep goggles, and significant staining might call for ciclosporin or amniotic membrane therapy. A systematic, evidence-based approach ensures each element of DED is addressed.
Clinical management should be dynamic: review, adapt, and escalate care based on patient response. Drawing from different stages of treatment is often necessary to meet individual needs.
Case Report – Multifactorial DED in a postmenopausal patient with Sjögren’s syndrome
This case highlights the complex interplay of hormonal, autoimmune, surgical, and therapeutic factors in a postmenopausal woman with Sjögren’s-related DED.
Patient A, a 58-year-old female, was referred in 2023 for a dry eye assessment following her return from overseas. She had a long-standing, multifactorial history of DED, with multiple contributing factors. Her ocular history included LASIK surgery, cosmetic blepharoplasty, antibody-positive Sjögren’s syndrome, and several courses of intense pulsed light (IPL) therapy.
She entered perimenopause at age 51 and reported abrupt onset of menopause at 55, following a Pfizer COVID-19 vaccination. Sjögren’s syndrome was diagnosed the same year. Current systemic medications included hydroxychloroquine (Plaquenil) and meloxicam (an NSAID).
Her treatment regimen had included both local and internationally sourced therapies: autologous serum eye drops, Regener-Eyes (a biologic drop not approved in Australia), Ikervis (ciclosporin), Thealoz Duo, Ivizia drops, and the Umay Rest neuromodulation device. She also used oral curcumin (Kurk), Bobby Brown mascara, and Blephadex (a tea tree-based lid cleanser).
On examination, tear meniscus height was borderline normal at 0.32-0.4 mm, suggestive of tear film collapse rather than high volume. Non-invasive tear break-up time (NITBUT) exceeded 15 seconds. Interferometry showed a severely reduced lipid layer, with increased viscosity on dynamic tear film analysis. Meibomian gland expressibility required moderate pressure; glands appeared structurally intact but obstructed at the lid margin.
Conjunctival staining was graded R2 and L3, with no corneal staining. Conjunctivochalasis was significant (Grade 3). Blinking was incomplete (Grade 3) with an elevated rate (>20 blinks/min). Lashes were clean, with no signs of Demodex, though excess lid margin froth suggested saponification. The Ocular Surface Disease Index (OSDI) score was 30, with symptoms worsened by wind, air conditioning, and screen use.
Clinical interpretation and management plan
Despite Patient A’s diagnosis of Sjögren’s syndrome, her tear meniscus height and NITBUT were within normal limits. This initially appears inconsistent with a severe aqueous-deficient profile, but is explained by her current regimen, which includes frequent instillation of high-viscosity, non-preserved artificial tears. This suggests that the aqueous deficiency component is relatively well managed.
However, interferometry and tear film analysis revealed a markedly deficient lipid layer and increased tear viscosity, indicating a mixed DED profile – both evaporative and aqueous-deficient
in nature.
Of all the topical treatments she was using, only Ikervis includes an oil component, and this is used only at night, offering minimal daytime lipid support. An oil-based lubricant was therefore recommended for daytime use.
Meibomian gland obstruction and reduced expressibility further supported the diagnosis of evaporative DED. Thermal lid therapy and gland expression were advised. Given the absence of demodex and the pro-inflammatory potential of tea tree oil, she was instructed to discontinue the Blephadex foam, which could be exacerbating her ocular rosacea. The presence of froth and telangiectasia indicated saponification and microbial imbalance, so Avenova (hypochlorous acid spray) was prescribed to reduce lid margin bacterial flora.
Conjunctival staining, without corneal involvement, can improve with both bacterial load reduction and anti-inflammatory agents. As Patient A had only recently initiated Ikervis (within three days), continuation of this therapy was supported.
Notably, she demonstrated incomplete blinking and a high blink rate, both of which contribute to mechanical friction and inflammation, potentially worsening CCH and meibomian gland dysfunction. Blink training and screen-use modification strategies were discussed.
Summary and recommendations
This case highlights the value of structured analysis in managing complex DED presentations. Clinicians should always correlate exam findings with patient-reported symptoms and treatment history (ensuring alignment between clinical signs and subjective experience). Assumptions must be reassessed, as normal-appearing findings may be influenced by intensive topical therapy.
Management should target each element of dysfunction – aqueous deficiency, lipid layer instability, blink mechanics, inflammation, and ocular flora – both individually and within a holistic framework. Unnecessary or counterproductive treatments (e.g., inflammatory cleansers in rosacea) should be discontinued. Treatment plans should be re-evaluated and adjusted at follow-up based on clinical response. By isolating contributing factors and tailoring interventions, even complex cases like Patient A’s can achieve meaningful improvements in comfort and ocular surface health. With the adjusted management plan, her OSDI score dropped to 8 – a reduction of more than two-thirds from the baseline.
Conclusion
Menopause significantly affects ocular health due to hormonal shifts, primarily causing DED driven by MGD, tear film instability, and inflammation. Beyond DED, menopause may also impact corneal health and elevate risks for glaucoma and cataracts.
Proactive management by eyecare professionals is crucial, involving thorough evaluation according to TFOS DEWS II guidelines and accurate subtyping. Treatment demands a tailored, stepwise strategy focused on MGD management and reducing inflammation. While systemic HRT isn’t a primary DED treatment, awareness of its potential ocular effects is necessary. An integrated approach, considering the patient’s overall menopausal health and potentially involving collaboration with other specialists, provides the best path to maintaining ocular well-being and quality of life during this transition.
More reading
Seeking sweet relief – identifying and managing dry eye in patients with diabetes
Aussie researchers lead global study on how dry eye impacts quality-of-life
Optometrist Aidan Quinlan lays out dry eye strategy in two case reports
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