Glaucoma is one of the leading causes of visual impairment and irreversible blindness in the world, with an estimated global prevalence of 76 million.1,2 The term glaucoma describes a heteronymous group of optic neuropathies characterised by structural damage to retinal ganglion cell axons at the level of the optic nerve head. This commonly results in progressive loss of the visual field and potential blindness unless treatment is initiated. The cornerstone of glaucoma management remains lowering of the intraocular pressure (IOP) via medications, laser treatment or surgical intervention.3
However, our understanding of glaucoma has evolved over the years, and the pathogenesis is now understood to be far more complex than simply IOP-related mechanical damage. Instead, risk factors for both development and progression of glaucoma are thought to be a complex interplay of genetics, neurodegeneration, oxidative stress, metabolic dysfunction, inflammation and compromised vascular supply. Not surprisingly, focus has turned to whether there are lifestyle changes such as diet, nutritional supplements, exercise, concurrent medical conditions, or use of systemic medications that may influence IOP or have an independent beneficial or deleterious impact on glaucomatous disease.
Armed with this knowledge, it is not uncommon for patients to enquire about certain lifestyle interventions that may influence their glaucoma. Therefore, it is important that eye care practitioners involved in glaucoma management are aware of latest evidence-based information.
Diet and Nutritional Supplements
Given the convincing findings from the Age-Related Eye Disease Study (AREDS) on supplement recommendations in slowing down progression of age-related macular degeneration (AMD),4 it is not surprising that the role of diet and supplements has also been examined in glaucoma management. Many forms of dietary modification, vitamins and supplements have been investigated and this section will focus on the most prevalent ones.
Flavonoids (Gingko Biloba)
Flavonoids are a diverse group of plant-based polyphenolic compounds, commonly found in dark chocolate, red wine, citrus fruits, berries and tea.5,6 One of the more well-studied flavonoid-containing supplements, in the context of glaucoma management, is gingko biloba. Gingko biloba is known to have inherent antioxidant, anti-inflammatory, neuroprotective and vasodilative properties.7,8 Its benefits in peripheral vascular, cardiovascular and cerebrovascular disease (such as Alzheimer’s disease) have been well-studied.7 Animal models have identified that gingko biloba may have both a pressure-lowering impact and neuroprotective effect on retinal ganglion cells.7
In human studies, ginkgo biloba appears to have beneficial effects on glaucoma with respect to both preventing progression and potentially improving performance on visual field testing. In 2003, Quaranta and colleagues8 published a double-blind crossover study, in which 27 patients with bilateral normal tension glaucoma (NTG) and progressive visual field defects were randomised to receive either placebo or gingko biloba extract 120mg daily for four weeks. These two groups were then washed out over eight weeks, and the treatments subsequently crossed over. Visual field testing was performed at baseline and then three times throughout the study – at the end of each treatment period, as well as at the end of the washout period.
While there were no statistically significant differences in mean deviation (MD) and corrected pattern standard deviation (CPSD) from baseline after the placebo treatment, there were significant improvements in both indices after the use of gingko biloba supplementation – average improvements in MD up to 2.77dB and in CPSD up to 2.83dB were detected. The use of gingko biloba was overall well-tolerated with no ocular or systemic side effects.8
As per previous animal studies, this improvement in perimetry appeared to be independent of IOP – no significant changes in IOP were noted throughout the entire study.8 The exact mechanism by which visual field improvement occurred was not clear but was hypothesised to be due to either increased blood flow, improved cognitive function and concentration during visual field testing (via increased cerebral blood flow) or enhanced neuroprotection.8 Improvement in perimetry had also washed out after eight weeks of discontinued gingko biloba use, indicating that long-term use of this agent is likely required to sustain the beneficial effect. Further longitudinal work is required to fully establish this. Nonetheless, gingko biloba certainly appears to offer some protective effect in glaucoma, particularly in potentially slowing down functional progression rate,9 and it is commercially available for easy access.
Other flavonoids, which have been recently studied and have shown some positive neuroprotective effects in animal models and small patient studies, include Erigeron breviscapus hand-mazz (EBHM), epigallocatechin-gallate (ECCG) and black currant anthocyanins (BCAC), with each of these showing some form of improvement in visual field results, reduced field progression and/or reduced IOP in patients with established glaucoma.7
Carotenoids (Saffron)
Similar to the flavonoids, carotenoids are naturally occurring in many plants, and their unique pigment provides the yellow, orange and red colours in fruits, vegetables and flowers.6 The carotenoid agents, lutein and zeaxanthin, are also naturally occurring within the macular region, and the use of these as supplements in AMD has been well-documented.4
Saffron contains high concentrations of carotenoid derivatives (crocin and crocetin) and its antioxidative properties in glaucoma management were investigated in a double-blind randomised study conducted by Jabbarpoor Bonyadi and colleagues.10 Fifty patients with stable (based on visual field and fundus examination) and medically-treated primary open angle glaucoma (POAG) were recruited and randomised to receive either saffron (30mg/day in aqueous form) or placebo. Primary endpoint was based on IOP only, with Jabbarpoor Bonyadi hypothesising that oxidative stress at the level of the trabecular meshwork interferes with, and reduces, aqueous outflow.10
Patients who received saffron in the study achieved a mean reduction in IOP of 2mmHg by the end of the four week period (compared to no change in the placebo group), however IOP returned to baseline after one month of discontinuation.10 In addition to a small sample size and short follow-up period, there was still a relatively large standard deviation and range of IOPs in the saffron group. Higher concentrations of saffron can also induce more systemic adverse effects – less than 1.5 grams per day is generally thought to be safe, although some reports of vomiting, nausea and diarrhoea have been reported at this level. Toxicity has been reported at over five grams per day.10
Additionally, saffron is one of the most expensive spices in the world and, in a lifestyle intervention pilot study conducted by Hecht and colleagues,11 incorporating the use of saffron among other lifestyle changes showed no significant reduction in IOP after four weeks. The clinical evidence for saffron is relatively weak and does not necessarily justify its cost, hence its use as a supplement in glaucoma management is not generally recommended.
Nicotinamide/Niacinamide (Vitamin B3)
Nicotinamide (also known as niacinamide) has recently shown significant potential as a novel treatment for glaucoma. It was postulated as a neuroprotective agent for glaucoma in 2017 by Williams and colleagues.13 In animal studies, they identified that mitochondrial dysfunction within the retinal ganglion cells was a key component in glaucoma development and progression. Nicotinamide adenine dinucleotide (NAD+) plays a critical role in maintaining mitochondrial health and is therefore inherently neuroprotective. Williams’ team theorised that supplementing serum levels of NAD+ may protect the optic nerve head against elevations of IOP, particularly in individuals with certain genetic and mitochondrial mutations that might otherwise predispose them to developing glaucoma.13
Following on from this, Hui and colleagues12 conducted a crossover randomised clinical trial, which showed significant improvement in visual field parameters and inner retinal function (where inner retinal dysfunction is a hallmark of glaucoma) in patients treated with nicotinamide. This study recruited 57 patients with early-to-moderate glaucoma and randomised them to receiving either a placebo or nicotinamide (NAM, the precursor to NAD+; Figure 1) for 12 weeks. The dosage of NAM was doubled from 1.5g/day to 3.0g/day at the six-week mark. After 12 weeks, the two cohorts swapped treatments but followed the same dosing of NAM (that is, six weeks of NAM 1.5g/day, then six weeks of 3.0g/day). NAM is the water-soluble amide version of Vitamin B3 and was commercially available at the time of the study (Blackmores Insolar). IOP, visual acuity (VA), full-threshold automated perimetry (SITA Standard 24-2) and electroretinogram (ERG) were assessed throughout the study. Adherence rates were high (greater than 94%, even with twice daily dosing of nictoniamide) and only mild adverse effects were reported (generally mild gastrointestinal symptoms and nausea).
While there were no statistically or clinically significant differences in IOP or VA between the treated and control groups, a greater proportion of patients on high-dose NAM showed an improvement in visual field mean deviation (MD) by >1dB on automated perimetry compared to the control group (27% vs 16%); similarly, fewer subjects demonstrated a reduction in MD (4% in the NAM group vs 12% in the control group).12 Impressively, there was also significant improvement in inner retinal function on ERG testing in the high-dose NAM cohort compared to placebo, even after only 12 weeks of NAM supplementation. Further studies are underway to show if these improvements are sustained over time, NAM shows promise as a treatment independent of IOP change which does not simply slow the rate of glaucoma progression but rather, may reverse disease and improve visual function.12
In discussions with patients, it is important to ensure that eye care practitioners recommend the equivalent form of NAM as that used in the study – Vitamin B3 in the form of niacin or nicotinic acid is known to cause more potential systemic side effects (such as gastrointestinal upset and facial flushing) as opposed to nicotinamide.12 Vitamin B3 can also be found naturally in foods such as fish, poultry, red meat, nut/seeds and legumes (Figure 2) and high dietary intake of these should be discussed.
Other Vitamins and Minerals
Other vitamins, such as vitamins A, C, D and E, have been investigated in glaucoma management, given their antioxidative and neuroprotective roles in other ocular and systemic diseases. However, these clinical trials and studies have generally been small-scale and have generated conflicting results with respect to whether they actually influence IOP or retard glaucoma progression.5,7,15 Certainly, there is evidence that diets rich in green, leafy vegetables (which contain high levels of nitrates and nitric oxide) are associated with reduced odds of glaucoma and this, in lieu of using vitamin supplements, should always be discussed and encouraged with patients.5,7
A study conducted by Wang, Singh and Lin16 also showed that high intake of supplementary calcium (>800mg/day) and iron (>18mg/day) may be associated with increased risk of glaucoma development, with Wang and colleagues hypothesising that these compounds accumulate in the body and promote oxidative stress and cell death (apoptosis). However, the study was limited by a high level of self-reported bias (that is, subjects were asked about a diagnosis of glaucoma and did not actually undergo an ophthalmic examination) and it was not possible to fully exclude that an original diagnosis of iron or calcium deficiency may in fact have been the original risk factor for glaucoma.16 It is therefore, reasonable for glaucoma patients to continue with the use of iron and calcium supplements at lower concentrations and in accordance with the current Recommended Daily Intake (RDI) guidelines issued by the National Health and Medical Research Council (NHMRC), which takes into account both dietary and supplementary intake (<1,000 to 1,300mg/day for calcium, and <8mg/day for iron, except for females during menstrual stages of life).17
Essential Fatty Acids (Omega-3 and Omega-6)
The role of the essential fatty acids (EFA), omega-3 and omega-6, in glaucoma management is not well-established. These are known to play a role in modulation of blood flow and maintaining cellular health in the rest of the body.5 Some studies have identified that high consumption of EFAs may increase risk for POAG, while others have found a reduction in the IOPs of patients with pseudoexfoliative glaucoma and NTG.7 The ratio of omega-3 to omega-6 intake may also influence risk, with a greater ratio of omega-6 to omega-3 potentially being beneficial and an inverse ratio associated with higher risk.5,15 Given that increased risk was associated with the highest quartiles of intake of EFAs,5 emphasis should again be placed on following the NHMRC RDI of omega-3 and omega-6.17
Caffeine
The link between caffeine, glaucoma risk and glaucoma progression has been tenuous at best.7 Some studies have detected small increases in IOP by 1-2mmHg for 90-120 minutes after coffee consumption.18,19 Consuming more than three to five cups of coffee a day does appear to be correlated with increased risk of developing glaucoma, particularly in certain sub-groups of patients – specifically, those with a positive family history of glaucoma and those with pseudoexfoliation syndrome.5,9,15 In patients with established POAG, excessive coffee consumption could be linked with increased risk of progression18 and it is therefore worth discussing with all glaucoma suspects and glaucoma patients the need to moderate caffeine intake. Interestingly, the impact of hot caffeinated tea seemed to be different from coffee – tea generally contains less caffeine than coffee and has a higher concentration of flavonoids which, as previously discussed, may offer a protective effect against glaucoma.5
Alcohol
In a similar fashion to caffeine intake, the relationship between alcohol consumption and glaucoma is unclear, with some studies finding no association, others a negative impact and, in some cases, a positive effect (via dehydration and reduced aqueous production).5,7,19 The conflicting evidence in the literature likely relates to individualised tolerance and metabolism of alcohol,7 as well as the form of alcohol – for example, red wines such as Cabernet Sauvignon and Pinot Noir contain a high concentration of flavonoids.5 In the interest of general health, alcohol consumption in moderation should be encouraged.
Exercise and Other Physical Activity
Aerobic Exercise
There is a high level of consensus in the literature that a moderate degree of aerobic exercise on a regular basis has a beneficial effect on IOP.5,7,15,18-20 Theories for this effect include release of nitric oxide by muscles, which helps to increase aqueous outflow through the trabecular meshwork; increased plasma osmolarity with a subsequent ‘dehydrating effect’; and increased blood circulation which would lend itself to improved perfusion to the optic nerve head.7 IOP reductions with aerobic exercise have been reported to be as high as 8mmHg in normal individuals, and as high as 13mmHg in patients with glaucoma,19 although IOP tends to return to baseline after 40 minutes.20 Additionally, the level of IOP reduction seems to be dependent on the intensity of the aerobic activity and level of fitness – those with a self-reported low fitness level or previous sedentary lifestyle seemed to generate the greatest reduction in IOP.5,15 However, as an individual became conditioned to exercise, the magnitude of reduction appeared to taper off.20
Overall, baseline IOPs of individuals who perform moderate exercise on a regular basis appear to be lower.20 On the other end of the scale, however, exhaustive or very high level intensity aerobic exercise may be associated with a greater prevalence of glaucoma and could be due to increased oxidative stress and inflammation.5 Thus, the general recommendation is to perform a moderate amount of aerobic activity on a regular basis to optimise IOP and lower the risk for glaucoma development.
Specific care also needs to be taken in individuals with pigment dispersion syndrome – ‘pigment showers’ and subsequent IOP elevation can occur during exercise, resulting in temporary blurred vision, headaches and haloes afterwards.21 Pigment dispersion patients should therefore be screened specifically for the presence of these symptoms following exercise, and in this situation either pilocarpine or YAG laser peripheral iridotomy (LPI) has been postulated to help reduce posterior iris bowing and mitigate the risk of post-exercise IOP elevation.22
The impact of exercise-induced IOP reduction in slowing progression in patients with established glaucoma is less clearly understood. One study which looked at this was conducted by Agrawal23 in 2015, wherein he recruited 90 patients with newly diagnosed POAG and divided them into three groups. Two groups were placed on topical treatment only, and the third group was commenced on medical treatment combined with aerobic exercise 30 minutes a day. A greater degree of IOP reduction was seen in the combined therapy group (9mmHg reduction) versus the medication only groups (6mmHg reduction).23 However, this was a small study and there were no further details provided as to what starting IOPs were and/or what form of aerobic exercise was prescribed.
Another likely beneficial effect of moderate exercise in glaucoma patients is the well-documented positive impact this can have on mood and stress.24 While eye care practitioners are rightly focussed on trying to stabilise functional and structural progression, it is imperative to recall that the diagnosis of a chronic and potentially vision-threatening condition can have a significant impact on an individual’s mental health and bring about symptoms of depression or anxiety. Aerobic exercise in glaucoma management may, therefore, serve more than one benefit – that is, it may improve IOP control and also quality of life.
Isometric Exercise and Weightlifting
Unlike aerobic exercise, in which various muscles are actively being trained to change length, isometric exercise involves holding a certain position to contract a specific muscle or muscle group. The goal of isometric exercise is to build muscle strength in a similar way to weightlifting.5 Isometric exercise and weightlifting have been known to transiently increase IOP by up to 4-5mmHg, although there is a fairly rapid return to baseline once ceased.15,19 In patients with established moderate-to-severe glaucoma, the potential influence of isometric exercise and weightlifting on IOP control should be discussed, given the impact this may have on glaucoma progression.
Yoga
Yoga has again been extensively investigated in several studies with respect to its impact on glaucoma risk and progression. Transient elevations of IOP can be as high as 11-16mmHg, especially with head-down poses such as Salamba Sirsasana (supported headstand), Adho Mukha Shvanasana (downward facing dog) and Uttanasana (forward fold)7,15,18 (Figure 3). Fortunately, the increase in IOP is transient and only sustained for the duration of the pose, with studies suggesting a return to normal IOP after five minutes.15 Nonetheless, in patients with evidence of progressive glaucoma despite seemingly good IOP control, it may be worth discussing amendment of yoga practices to eliminate head-down poses.
Swimming
Swimming with tight-fitting goggles has been identified as a cause of temporary IOP elevation,7,20 although there is some debate as to whether this is only significant in patients with established glaucoma as opposed to normal individuals.5 IOP tends to normalise after removal of the goggles, nonetheless in patients with moderate-to-severe glaucoma it is generally recommended to avoid tight-fitting elastic bands and eye pieces.20
Other Lifestyle Interventions
Neckties
Tight fitting neckties appear to cause a temporary elevation of IOP in both normal and glaucomatous patients, lasting for approximately three minutes, however the effect then normalises by 15 minutes.25,26 The impact of tight neckties on glaucoma progression is therefore likely to be very low. Depending on when the necktie was secured, there may be an impact on IOP measurements and this should be considered during an eye examination.18
Temperature
Excessive sweating (such as in saunas) and dehydration can cause a temporary reduction in IOP.20 Conversely, symptoms of Raynaud’s disease and poor peripheral vascular circulation are worsened in cold environments and this in turn may negatively impact NTG patients.20
Altitude
In altitude sports, such as mountain climbing, IOP generally tends to increase with higher altitudes which may be partially due to increased corneal thickness.20 IOPs tend to return to baseline once an individual returns to normal altitude.20 Acute mountain sickness (a mild form of altitude sickness) can also affect blood flow to the optic nerve and result in temporary hypoxia to the optic nerve. Commercial aircraft cabins are generally pressurised and therefore, flying at a high altitude does not influence IOP.20
Wind Instruments
A number of individual cases and small case studies have shown that high-resistance wind instruments, such as brass instruments and woodwind instruments (particularly reeded and double-reeded instruments such as the clarinet and oboe), can induce a temporary elevation of IOP for the duration that the instrument is played, similar to the impact of a Valsalva manoeuvre.20 ‘Regular’ playing of woodwind and brass instruments for 10-20 minutes seems to increase IOP by an average of 1.5-2.5mmHg,27 however this plateaus after approximately two minutes of playing, after which IOP declines slightly.28
On the other hand, playing a sustained high-pitch note with maximal exertion can induce an average IOP elevation of 6-7mmHg and would put the majority of players into the ocular hypertensive range (>21mmHg).28 These elevations, variations and peaks in IOP may play a significant role in glaucoma risk and progression, and the importance of regular glaucoma screening and monitoring needs to be emphasised and discussed with individuals who play brass and woodwind instruments.
Systemic Conditions and Medications
Obstructive Sleep Apnoea
Obstructive sleep apnoea (OSA) is defined as repeated complete or partial obstruction of the upper airways during sleep that results in cessation of breathing and subsequently leads to hypoxia.29,30 It has been hypothesised that hypoxia and/or increased oxidative stress from OSA results in reduced perfusion to the optic nerve head, and OSA may therefore be an independent risk factor for glaucoma.9 Certainly, there is evidence in the literature that suggests a higher incidence of OSA in glaucoma patients, and vice versa.31-33
Moreover, Yamada and colleagues34 recently found that in a group of 124 glaucoma patients, there was a greater rate of progression of visual field defects (measured by mean deviation) in patients with OSA compared to those without OSA. It would therefore be reasonable to infer that detection and treatment of OSA would have a positive flow-on effect on glaucoma management.
In general, it has been recommended that patients with a history of glaucoma or ocular hypertension should be screened for OSA symptoms to determine if a formal sleep study is indicated, and conversely, patients with OSA should be encouraged to undergo regular eye examinations with their eye care practitioner.32 Questionnaires such as the Epworth Sleepiness Scale (Figure 4) can be useful for screening purposes although there are other physical characteristics and observable sleep behaviours that need to be formally assessed.31 Side-sleeping or sleeping with mild head elevation is likely to be beneficial for both glaucoma and OSA.
