The emerging science of psycho-neuro-endocrine-immunology and glaucoma management

Psycho-neuro-endocrine-immunology (PNEI) is an interdisciplinary field that explores the complex interactions between the psychological processes, nervous system, endocrine system, and immune system. This field of mind-body medicine examines how these systems communicate and influence each other, particularly in the context of health and disease. Psychological states can influence biological processes and vice versa, and this is especially relevant in chronic degenerative diseases like glaucoma. In particular, psychological stress can trigger two key hormonal pathways – the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) axis.

HPA Axis: The hypothalamus releases corticotropin-releasing hormone (CRH) in response to stress. CRH stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH prompts the adrenal glands to produce cortisol, the primary stress hormone. Elevated cortisol levels can increase intraocular pressure (IOP), which is a significant risk factor for glaucoma. Elevated cortisol levels are also detrimental to neurons in the hippocampus, and cognitive decline with loss of memory has been linked to elevated cortisol. This is a key factor implicated in neuro-degenerative diseases. Additionally, glaucoma patients are already “high steroid responders,” and increased levels of endogenous cortisol can lead to significant elevations of IOP.

SAM Axis: In response to stress, the sympathetic nervous system activates the adrenal medulla. The adrenal medulla releases catecholamines, including adrenaline (epinephrine) and noradrenaline (norepinephrine), and these can influence IOP as well as cause vasoconstriction, leading to a decrease in retinal and optic nerve blood flow, which can be deleterious for the retinal ganglion cells (RGCs) (especially relevant for normal pressure glaucoma).

Chronic stress can also lead to the overproduction of pro-inflammatory cytokines, such as IL-6 and TNF-α. These cytokines can contribute to neuroinflammation and apoptosis of RGCs. Inflammation also causes oxidative stress, which further damages RGCs and contributes to the progression of glaucoma.

Thus, stress can be both a causative as well as a contributing factor for glaucoma. As the glaucomatous optic neuropathy worsens, the fear of blindness exacerbates the stress factor, which in turn leads to further rise of cortisol, catecholamines, and neuroinflammation – this creates a self-perpetuating vicious cycle with grave implications for the overall health-related quality of life and progression of glaucomatous optic neuropathy.[1] All these factors implicated in RGC apoptosis further worsen with the “aging” process, and there are practically no pharmacological drugs which can be used to lower cortisol, catecholamines, or inflammatory mediators in glaucoma patients.

Glaucoma patients are thus in a state of physiological dysfunction – “allostatic overload.” To address this issue, there is an unmet need for mind-body therapies to counter the stress response and target non-IOP mechanisms to deliver a holistic management for glaucoma patients.

Breathing techniques for better health

Slow controlled breathing exercises can achieve physiological and psychological benefits and can be useful for glaucoma patients. Slow, controlled breathing (6 breaths per minute) activates nasal and vagal afferents that stimulate cortical and brainstem networks. This stimulation has been shown to enhance autonomic balance by increasing parasympathetic activity while decreasing sympathetic arousal. These changes are reflected in an increase in heart rate variability (HRV), a key marker of autonomic flexibility and vagal tone.[2]

A six-month program incorporating yogic pranayama and diaphragmatic breathing (YPDB) in patients with primary open-angle glaucoma (POAG) showed a significant reduction in IOP by 5–6 mmHg when practiced in addition to their regular anti-glaucoma medications compared to those on medications alone.[3]

The “365 breathing technique,” which involves taking six breaths per minute for five minutes, three times a day, is another structured approach that has shown promise. In a randomized trial, patients practicing this technique for six weeks exhibited improved parasympathetic tone, decreased serum cortisol, and significantly lowered IOP compared to controls.[4]

Mindfulness meditation focused on breath

Meditation is a mental practice that involves training, attention, and awareness to achieve emotional calm and clarity and enhance overall wellbeing. Meditation practices can be broadly categorized into focus-attention meditation (e.g., breath awareness or mantra repetition), open-monitoring meditation, compassion-based meditation, and transcendental meditation. Mindfulness meditation focused on breath has been found to be especially useful for glaucoma patients.

The mechanism through which meditation benefits glaucoma patients is multifaceted and it actually serves as a “polypill” for glaucoma.[1] Regular meditation practice can positively impact several pathological processes associated with glaucoma and reverse the key changes associated with activation of the HPA and SAM axis, as well as impact neuroinflammation. Meditation works through the release of two key molecules – nitric oxide and melatonin, which leads to increased trabecular outflow and enhanced ocular blood flow. At the cellular level, meditation upregulates mitochondrial function, confers neuroprotection by enhancing brain-derived neurotrophic factor (BDNF), and decreases neuroinflammation by decreasing TNF alpha and IL6. It leads to a reduction of cortisol and reversal of autonomic dysfunction with an increase in parasympathetic activity and improves the overall quality of life of the patients as well as their caregivers. Glaucoma patients often have associated systemic disorders such as diabetes, hypertension, and coronary artery disease, and meditation can also serve as a useful adjunct for reversing end-organ damage associated with these disorders and reducing the risk of mortality.[5,6,7,8,9]

Optimizing healthspan

Meditation focused on breath offers an evidence-based, safe, and holistic adjunct to conventional glaucoma care, which can be adopted by patients across all age groups.[10] It addresses several modifiable risk factors beyond IOP, including stress, inflammation, oxidative damage, and vascular dysfunction. These practices are well tolerated, cost-effective, and empower patients as well as their caregivers to positively cope with glaucoma – a lifelong journey with a sight-threatening disease. Simple instructions can be given to the patients – find a quiet place of solitude, sit comfortably with your back straight, close your eyes, and focus on a point on the tip of the nose between the eyebrows, and just be aware of your natural breath while slowly inhaling and exhaling. As your thoughts drift, gently bring your attention back to the breath. Starting with 5–10 minutes and gradually increasing to 30–45 minutes can be recommended.

Incorporating meditation practice over the long term can improve the overall health-related quality of life of our patients. Recent studies have shown that individuals with glaucoma actually have accelerated aging, and meditation can slow cellular aging, potentially exerting a profound impact on the course of the disease.[11,12] As healthcare providers, our success goal should not only be about achieving target IOP but also optimizing the healthspan of glaucoma patients by encouraging lifestyle changes that promote positive health and wellbeing for both our patients and their caregivers, helping them thrive and flourish throughout the “long marathon run” – a life with glaucoma.[13,14,15]

About the author

Dr Tanuj Dada MD, FRCSEd

Dr Tanuj Dada is currently Professor of Ophthalmology and Head of Glaucoma Services at RP Centre for Ophthalmic Sciences, AIIMS-New Delhi. He completed his undergraduate and postgraduate training from the All India Institute of Medical Sciences (AIIMS), New Delhi and was awarded the gold medals for best undergraduate and best postgraduate in ophthalmology. He has over 350 research publications in peer reviewed indexed journals and has authored 5 textbooks on glaucoma. He is recipient of the special recognition award by World Glaucoma Association and is currently serving on the Board of Governor’s of the World Glaucoma Association and on the Board of Directors of the Asia Pacific Glaucoma Society. He is on the editorial board of the American Journal of Ophthalmology, associate editor Journal of Glaucoma and is the founding & Chief Editor of the Journal of Current Glaucoma Practice. He chairs the scientific program planning committee for the World Glaucoma Congress (USA 2025) and Asia Pacific Glaucoma Congress (Singapore 2026). He has innovated several new techniques of glaucoma surgery and pioneered the research on meditation and glaucoma.