The impact of different forms of exercise on intraocular pressure, blood flow, and the risk for primary open angle glaucoma

Abstract

Primary open angle glaucoma (POAG) is a chronic disease characterized by progressive optic nerve damage and irreversible loss of vision, often diagnosed at late stages. Elevated intraocular pressure (IOP) is the major risk factor for its onset and progression while older age, myopia, genetic factors, blood pressure (BP), and reduced ocular blood flow (OBF) have also been linked to the disease. Different forms of exercise are known to have significant, but variable, effects on IOP, BP, ocular perfusion pressure (OPP), OBF and oxygen metabolism, and ultimately the risk for development and progression of POAG. While population-based studies lack agreement regarding the relationship between exercise and POAG status, data suggests that resistance training causes a short-term increase in IOP, BP, and OPP. Conversely, aerobic exercise has been shown to cause a short-term decrease in IOP and increase in BP and OPP. Research also suggests that following an exercise program over an extended period may lead to a long-term decrease in IOP, however its cessation results in a prompt return to baseline levels. Data suggests normal vascular autoregulation ensures minimal change in OBF following extended exercise unless OPP rises ~70% above baseline. Although exercise may alter IOP, BP, and OBF, both acutely and chronically, it is currently uncertain if physical activity significantly alters risk for the onset and progression of POAG.

Introduction

Glaucoma is one of the most common causes of blindness worldwide and is characterized by progressive optic nerve damage resulting in irreversible visual impairment. The global prevalence of glaucomatous disease is expected to increase from 76.0 million in 2020 to 111.8 million in 2040.¹ Primary open-angle glaucoma (POAG) is the most common form of the disease, primarily affecting people over the age of 40.² Risk factors for POAG include elevated intraocular pressure (IOP), myopia, African descent, low ocular blood flow (OBF) and ocular perfusion pressure (OPP), systemic hypertension, and advanced age.^1,3–5 Although optic nerve damage in POAG is most often associated with elevated IOP, blood pressure (BP) status, poor vascular health, and impaired oxygen metabolism have all been shown to contribute to the disease process in many patients.^2,4–6

There is a void of data on exercise and the long-term risk for POAG. Current data frequently originate from subanalysis of larger studies with different aims and/or are small pilot studies with limited samples. Related investigations also use different forms of exercise over various periods of time in conjunction with different definitions of POAG and clinical endpoints. For example, the intensity level of exercise has been previously correlated with a lower odds of POAG onset according to the National Health and Nutrition Examination Survey (NHANES).⁶ However, some population-based studies have found that exercise has little to no association with the prevention of POAG or its subsequent progression.⁷ Data are therefore highly diverse and lack consensus. There is a further need to account for multiple overlapping factors such as treatments and diet that are not uniform within published studies. In a void of controlled large-scale longitudinal studies on POAG status, examining the impact of different forms of exercise on its risk factors, including IOP, BP, and OBF and oxygenation may help inform on POAG and improve options for enhancing disease management.

Physical activity significantly influences many of the physiological mechanisms involved in the pathophysiology of POAG. Mechanistically, various forms of exercise are known to alter IOP, BP, OPP, and OBF, as well as oxygen metabolism. Some forms of exercise might naively be expected to be preventative of POAG as they are known to lower IOP and BP, reduce diabetes risk, and increase oxygen metabolism. This is due to the fact that the physiological factors involved are complex and occur across the entire body, including changes in the body’s fluid pressures including IOP and BP, release of nitric oxide (NO), alterations to oxygen metabolism, improved mitochondrial function and/or cellular stress responses, and mediation of endothelin-1 (ET-1).^8–12 The totality of changes to these factors on risk for POAG disease onset and progression, however, remain uncertain.

The long-term impact of exercise on these factors differ based on the various forms and duration of activity, and for the length of time exercise is maintained throughout life. For example, resistance training often causes a short-term increase in IOP, BP, and OPP while aerobic exercise results in a short-term decrease in these parameters.^13–20 The duration of activity also significantly influences impact of exercise on POAG risk factors. A regular exercise program over an extended period of time has been shown to result in a long-term decrease in IOP which persists if the program is consistently adhered to, but then returns to baseline upon its cessation.²¹

Although evidence supports the long-term benefits of exercise on general health, the short-term physiologic changes that occur during certain forms of physical activity may negatively contribute to POAG development. This review examines the available literature regarding different forms of exercise of POAG risk including aerobic exercise and resistance training and assesses their acute and chronic impact on physiologic parameters shown to play a role in glaucoma pathology, including IOP, BP, OPP, and OBF and oxygen metabolism.

Materials and methods

A comprehensive literature search on exercise and glaucoma was conducted through September 16, 2024, using PubMed, Embase, Ovid, Scopus, and Trip searches including the following keywords: exercise, activity, sports, workout, training, movement, exertion, intraocular pressure, glaucoma, blood pressure, blood flow, vascular density, retina, diagnosis, and progression. Articles were screened for relevance, and reference lists of relevant articles were also searched and cross-referenced for other relevant articles. Two independent reviewers (MS, JC) reviewed 104 articles and 51 of these articles were judged to include relevant information regarding physical activity and either hemodynamic parameters, glaucoma, or both, and were included in this review. Data were collected and organized using Microsoft Word (version 16.30), Microsoft Excel (version 16.30), and EndNote (X8.2).

Results

The effect of exercise on glaucoma status and progression

When assessing glaucoma risk, the literature often infers the impact of exercise rather than directly correlating specific forms of it with clinical outcomes. For example, researchers using the United States National Health and Nutrition Examination Survey found that subjects who typically stood or walked throughout the day as opposed to sitting had a 58% lower chance of being diagnosed with glaucoma.⁶ When comparing people who performed moderate vigorous activity as a part of their routine to those who did not, researchers found the group that exercised had a 95% lower chance of being diagnosed with glaucoma.⁶ These findings directly contrast with those from a Korean National Health and Nutrition Examination Survey population-based study with approximately 11,000 participants, which found that daily vigorous exercise was associated with higher glaucoma prevalence in men.²² Surprisingly, the same study did not find a statistically significant association between exercise and glaucoma diagnosis in women.²² Subjects who performed vigorous exercise 7 days a week were found to be at higher risk for glaucoma than those who only exercised 3 days a week. In addition, high-intensity exercise was more strongly associated with glaucoma diagnosis compared with moderate-intensity exercise.¹⁷ A study of the UK Biobank found that exercise, whether moderate or vigorous, had no association with glaucoma.⁷ The same study found that higher physical activity may be associated with a thicker macular ganglion cell inner plexiform layer although the clinical result of the study was unclear.⁷ Differences in these studies may stem from population size, characteristics, or methodology. Attenuation of effect, where true associations weaken in larger samples or when accounting for confounding, may also contribute to the varied results.

Concerning the progression of glaucoma, aerobic exercise may offer benefits to individuals with POAG, potentially slowing the advancement of the disease and safeguarding against neurological damage.²³ However, more research is needed to confirm these effects, especially over with longer duration of follow-up.²³ Randomized-controlled trials in rodents indicate exercise may shield aging retinas from oxidative stress and neuronal loss.^23–25 Clinical studies in humans substantiate the findings that exercise may independently slow glaucoma disease progression.^23,26–29 While further prospective studies are needed, evidence strongly supports that exercise may slow glaucoma disease progression.^23–29

Overall, population-based studies on exercise and glaucoma status currently provide conflicting results on the risk for POAG.^6,7,22 The complexities of accounting for diet, life-long exercise, and other risk factors limit conclusions on long term clinical outcomes.^{5–7,13–20} While no clear risk model has been derived from population-based studies, extended (time-based aerobic) forms of exercise have been shown to longitudinally decrease IOP and BP, two major risk factors for glaucoma.^{5–7,13–20} Although promising, current population-based data are insufficient to determine any role of various forms of physical activity in preventing the onset of glaucoma.^{5–7,13–20,22} Nevertheless, the substantial evidence in the literature specifically supports the role of aerobic exercise in slowing the progression of glaucoma, indicating that chronic aerobic exercise likely offers protection against the disease.^23–29

The effect of exercise on intraocular pressure (IOP)

Different forms of exercise have different and significant influence on IOP. Several studies have reported significant alterations during both aerobic and resistance training (Table 1). To understand the impact of exercise on POAG it is important to differentiate aerobic versus anaerobic exercise data and chronic versus acute effects.

Table 1.

Summary of studies investigating the relationship between intraocular pressure (IOP) and exercise.

Study	Subjects	Exercise Plan	Effect on IOP (mmHg)
Kawae et al.13	18 healthy male subjects	20 min bicycle at 70% ·VO2	−2.6
Qureshi14	7 healthy male subjects	Walking	−2.43±0.30
		Jogging	−3.85 ± 0.55
		Running	−4.0 ± 0.37
Vera et al.15	17 healthy male subjects	Four sets of bench press at 75% of the subject’s one-repetition maximum	0.9
		Four sets of bench press at 85% of the subject’s one-repetition maximum	1.4
		Four sets of bench press at 95% of the subject’s one-repetition maximum	2.9
Vera et al.16	26 (13 male; 13 female) healthy subjects	Isometric squat with medium load	1.6 higher compared to the low load
		Isometric squat with high load	1.5 higher compared to the medium load
Yeak Dieu Siang et al.21	45 (9 male; 36 female) healthy subjects	6-weeks exercise program with resistance training and aerobic exercise	−2.18 ± 2.25
Ma et al.30	123 (62 male; 61 female) patients with POAG	Cycling at moderate intensity (20% Wmax for 10 min) and high intensity (60% Wmax for 5 min)	−2.37 ± 2.67 after 10 min of moderate intensity
			−5.95 ± 3.80 mmHg after another 5 min at high intensity
Nie et al.31	25 (16 male; 9 female) patients with POAG	20-min run at moderate intensity	−14.20 ± 2.51
	22 (14 male; 8 female) healthy subjects		−14.51 ± 2.96

Aerobic exercise

Aerobic exercise is a type of exercise characterized by its effect on the cardiovascular system and reliance on oxygen. In each of the studies reviewed, aerobic exercise refers to either walking, jogging, or running at various intensities. In nearly all the studies reviewed, a decrease in IOP has been demonstrated during and shortly after aerobic exercise.^13,14,30,31 These decreases usually become larger as intensity raises, with data showing that only high-intensity aerobic exercise provides a decrease in IOP that is statistically significant.¹³ Kawae et al. found that IOP decreased significantly at an intensity level of 70% of VO2 max while there was no significant change in IOP after subjects underwent low and moderate-intensity aerobic exercise at 30% and 50% of their VO2 max.¹³ Aerobic forms of exercise performed over long periods of time may significantly reduce the overall risk for POAG through a chronic reduction of IOP.

In general, the literature to date is in agreement that aerobic forms of exercise cause significant decreases in IOP. Specifically, Qureshi demonstrated that the average reduction in a healthy subject’s IOP after walking was 2.43 ± 0.30 mmHg; this difference increased to −3.85 ± 0.55 mmHg when looking at subjects who jogged, and rose to −4.0 ± 0.37 mmHg in subjects who ran.¹⁴ Moreover, subjects with glaucoma demonstrated a larger magnitude of IOP reduction in comparison with normal subjects following exercise.¹⁴ Patients with glaucoma also experienced a larger magnitude and duration of IOP lowering in comparison with otherwise healthy subjects.¹⁴ Conflicting data has been provided by Vera et al. and showed an increase in IOP after subjects exercised to the point of exhaustion³²; however, this conclusion has not been further supported by other studies.

Although the ability of aerobic exercise to reduce IOP is widely accepted as supported by multiple studies, the process through which this occurs is not clearly understood. The three most plausible theories regarding the mechanism of this effect involve elevated blood plasma osmolarity, decreased blood pH, and elevated blood lactate.^33–36 During exercise, the plasma colloidal osmotic pressure increases as effect of sweat and loss of fluids, thus a reduction in the aqueous humor production and consequently IOP.^37,38 Sympathetic nerve stimulation caused by aerobic exercise has also been suggested to reduce IOP via morphological changes in the trabecular meshwork and Schlemm canal and increased outflow.³⁹

While more research is needed to better elucidate the mechanisms behind the effect of aerobic exercise on IOP lowering, available evidence indicates that this form of exercise may be most beneficial for patients with high IOP who are at risk for onset or progression of POAG.

Resistance training

Resistance training is a form of exercise characterized by muscular contraction in response to a form of resistance. In each of the studies reviewed, resistance training, whether isometric or isotonic, increased subjects’ IOP during and shortly after the activity.^15,16,40 The transient nature of these changes on IOP suggests that the effect of resistance training on ocular health would occur during the exercise.¹⁶ Similar to the manner in which the intensity of aerobic exercise affects change in IOP from baseline, the amount of weight used, even if the intensity remains the same, affects how far a subject’s IOP will rise above baseline.^15,16

Vera et al. assessed IOP in 17 healthy males before and after resistance training comprised of 4 sets of bench press to muscular failure with different loads (65%, 75%, 85%, 95% one-repetition maximum (1RM)). Performing the bench press exercise with 65% of the subject’s 1RM did not significantly affect IOP, despite the high intensity.¹⁵ However, performing sets with 75%, 85%, and 95% of the subject’s 1RM increased IOP by 0.9 mmHg, 1.4 mmHg, and 2.9 mmHg, respectively. These sets were all performed at the same relative intensity as each subject was said to have reached muscular failure. IOP levels returned to baseline shortly after recovery similar to the rate of return to baseline following aerobic exercise,¹⁵ thus indicating that IOP levels may also return to baseline quickly. Another study found that the level to which a subject’s IOP rose depended on the type of resistance exercise they were doing.⁴⁰ Squats caused a greater increase in IOP than military presses which caused a greater increase than bicep curls.⁴⁰ Yoga, a form of exercise that includes multiple isometric and isotonic contractions, has been shown to increase IOP acutely in both healthy and glaucomatous subjects.⁴¹ Each yoga position assumed by the subjects in this study (Adho Mukha Svanasana, Uttanasana, Halasana, and Viparita Karani) involved putting the head either flat on the ground, or down towards the floor.⁴¹ These findings are in line with others showing that changes in body position, whether it be from swimming or performing inverted headstands, can raise IOP.⁴²

The literature is without consensus on the effects of resistance training and IOP. While some studies identified a transient rise in IOP during resistance and isometric exercises,^15,16,40 others noted that isometric exercise resulted in an acute decrease in IOP (which may be correlated with hypocapnia) and that dynamic exercise resulted in a more pronounced acute decrease in IOP.⁴³ While findings differed for isometric exercise, dynamic exercise reduces IOP in both healthy and glaucomatous patients.⁴⁴ Overall physical fitness was associated with lower baseline IOP, but diminished acute IOP-lowering response to exercise; however, when exercise ceased, IOP returned to pre-training levels within one month.⁴³ Participating in an exercise routine that included both resistance training and aerobic exercise resulted in a long-term decrease in IOP.²¹ The routine in this study spanned 6 weeks and the mean IOP was reduced by 2.18 ± 2.25 mmHg at the conclusion of that period.²¹ However, this long-term decrease in IOP may be attributable to the aerobic exercise, resistance training, or a combination of both.

Many studies find high-intensity resistance training at sufficient load and exercises that involve laying down or inverting one’s head generally results in an increase in IOP,^{15,16,40–43} that has been suggested to be mediated by an increase episcleral venous pressure.^45,46 Therefore, it may be prudent for high-risk patients to limit or avoid engaging in training that involves heavy weight loads, breath-holding, or head-down position when at risk for POAG.

The effect of exercise on blood pressure

Exercise and BP share a complex relationship. BP is the force produced by blood against the artery walls and includes systolic (SBP) and diastolic (DBP) readings. These two measurements are used to calculate the mean arterial pressure (MAP) through the formula DBP+⅓(SBP – DBP).⁴⁷ Ocular perfusion pressure (OPP) is equal to: (2/3MAP-IOP), and represents the driving force of blood into the eye against the force of IOP.⁵ Understanding the relationship between BP, IOP, and OPP is, therefore, important in understanding the potential mechanistic risk or protection exercise may afford to ocular health

In most of the studies reviewed, engaging in exercise, whether aerobic, isometric, isotonic, or a mix of both, resulted in long-term reduction of SBP, DBP, and MAP (Table 2).

Table 2.

Summary of studies investigating the relationship between exercise and blood pressure.

Study	Subjects	Exercise Plan	Effect on blood pressure (mmHg)
Carlson et al.17	127 healthy and hypertensive subjects	Isometric resistance training for at least 4 weeks	SBP: −6.77±1.15 DBP: −3.96 ± .84 MAP: −3.94 ± .79
Ogbutor et al.48	200 pre-hypertensive subjects	Isometric handgrip exercises over 24 days	SBP: −7.48 ± .06 DBP: −6.41 ± 1.01 5 min post exercise: SBP: 8.60 ± 0.20 DBP: 7.33 ± 0.03
Cao et al.18	860 hypertensive subjects	Aerobic exercise	SBP: −12.26 ± 2.92 DBP: −6.12 ± 1.64
Conceição et al.19	Unknown	Dance therapy (aerobic exercise)	SBP: −12.01±4.07 DBP: −3.38 ± 1.44
Olea et al.49	11 hypertensive male subjects, 27 hypertensive female subjects	High intensity aerobic exercise on a bike over two months	SBP: −27.7 ± 18.9 DBP: No significant change
Cornelissen & Smart20	105 groups of healthy subjects (unknown exact)	Endurance training (aerobic exercise) over 4 weeks	SBP: −3.5 ± 1.2 DBP: −2.5 ± 0.8
	29 groups of healthy subjects (unknown exact)	Dynamic resistance training (isotonic) over 4 weeks	SBP: −1.8 ± 1.8 DBP: −3.2 ± 1.2
	5 groups of healthy subjects (unknown exact)	Isometric resistance training over 4 weeks	SBP: −10.9 ± 3.5 DBP: −6.2 ± 4.2
	14 groups of healthy subjects (unknown exact)	Combination of above 3 over 4 weeks	SBP: No significant change DBP: −2.2 ± 1.7corne

DBP: diastolic blood pressure; MAP: mean arterial pressure; SBP: systolic blood pressure, primary open-angle glaucoma: POAG.

In a study measuring the changes in subjects’ SBP and DBP over a 2-month period during which they participated in high-intensity aerobic exercise, Olea et al. found that SBP, on average, decreased by 27.7 mmHg, but DBP underwent no significant change.⁴⁹ Following an exercise program over an extended period of time has been demonstrated to lower DBP in other studies.¹⁸ Ogbutor et al. measured not only the long-term effects of engaging in an exercise program involving isometric handgrip exercises, but also the short-term effects on blood pressure immediately after subjects completed the exercise.⁴⁸ Over 24 days, the subjects’ SBP and DBP dropped by an average of 7.48 mmHg and 6.48 mmHg, respectively. However, when measuring subjects’ BP 5 min after exercise, the SBP and DBP went up by an average of 8.6 mmHg and 7.33 mmHg, respectively.

This short-term response of BP to exercise occurs primarily because of the increased demand for oxygen by working muscles during exercise. Physiologically, to boost oxygen delivery, heart rate increases, which usually causes increased BP despite the vasodilation that may occur in the arteries.⁵⁰ However, a sustained exercise program produces a decrease in vascular resistance which reduces the pressure level required to achieve a given level of OBF, thereby resulting in a long-term decrease in BP.⁵¹

The effect of exercise on ocular perfusion pressure and ocular blood flow

As OPP is calculated from IOP and BP, it also may be affected by various forms of exercise that impact fluid balance, HR, and/or BP. A higher baseline OPP represents a stronger force of blood delivery to the eye and a low OPP may contribute to decreased ocular perfusion and exacerbation of glaucomatous optic nerve damage.^5,52 Exercise has also been shown to greatly affect retinal vessel density and choroidal thickness in children whose eyes are either emmetropic or myopic, thus suggesting that exercise may influence both OPP and OBF.⁵³ Aerobic exercise and resistance training have been shown to increase the OPP of both healthy subjects and glaucoma patients; however, this often results in only a minimal increase in OBF because of vascular autoregulation.^{5,33,43,54,55}

Vascular autoregulation may mitigate alterations in OBF during fluctuations in OPP in healthy individuals, with less active autoregulation potentially putting persons at risk for POAG. Lovasik et al. used laser Doppler flowmetry and electronic sphygmomanometry to measure choroidal blood flow and OPP respectively after volunteers finished biking exercise. In this form of exercise, while OPP increased by approximately 43%, choroidal blood flow stayed within 10% of baseline.⁵⁵ This suggests that vascular autoregulation, where blood vessels dilate or constrict in order to keep blood flow constant when perfusion pressure changes, keeps OBF close to baseline while OPP experiences a significant increase.³³ Importantly, autoregulation fails at OPP levels greater than 70% above baseline.⁴³ Blood flow in the retina and optic nerve head (ONH) undergoes autoregulation in response to a change in OPP; however, the choroid undergoes a weaker form of autoregulation as choroidal blood flow has been shown to increase after exercise.^33,44 Okuno et al. used scanning laser Doppler flowmetry and laser speckle flow-graphy in order to measure blood flow in the choroid and retina after exercise. While the retina had a transient increase in blood flow 15 min after exercise, the choroid had an increase in blood flow up to 60 min after exercise.⁵⁶ Therefore, exercise has different effects on different parts of the eye. While acute exercise usually only increases OPP acutely and typically does not significantly affect blood flow in the retina and ONH, exercise may have a more profound effect on the choroid.^33,56 Previously aerobic exercise led to a short-term increase in OPP and ocular blood flow in subjects with POAG.⁵⁷ Conversely, OBF significantly decreased after people from various fitness levels completed a marathon, possibly due to post-marathon dehydration that can result in retinal vein occlusions.⁵⁸ Retinal vascular plexus density, median choroidal thickness, and SBP and DBP significantly decreased within one hour after finishing the marathon, while median macular and retinal nerve fiber layer thicknesses significantly increased (all p < 0.01).⁵⁸ The decrease in OBF may also occur because vascular autoregulation in the eye has been shown to fail once the OPP reaches 67% above baseline which then results in an increase in OBF.³³

Exercise impacts NO which is a known vasodilator, while the role of NO and ET-1 are both involved in mediating the effects of exercise on OBF and OPP. Specifically, increased NO after exercise has been shown to induce vasodilation at the level of ophthalmic and ciliary arteries,⁵⁹ and increased outflow of aqueous humor.^8,60 On the other hand, ET-1 during isometric exercise has been shown to induce an increase in OPP.¹¹ Interestingly, both impairment in NO production and elevated ET-1 plasma concentration have been shown to increase risk of glaucoma onset and progression.^9,61 Chronic aerobic exercise may also lead to improved mitochondrial function and/or cellular stress responses.¹²

Current literature suggests that chronic aerobic exercise lower IOP and negligibly increase OBF in patients with glaucoma, but the clinical impact on glaucoma risk is uncertain. Weightlifting and other forms of acute intense isometric exercise may increase IOP and potentially elevate POAG risk. Carefully designed longitudinal studies are needed to reveal if increasing physical activity chronically results in a significant increase in basal OBF, OPP, and/or other protective measures against glaucoma POAG.

Acute versus chronic effects of exercise on POAG risk

As population-based studies investigating the relationship between exercise and glaucoma yield contrasting results, it is more favorable to evaluate the acute effect of exercise on risk factors for glaucoma, which may affect the chronic risk of developing POAG.

Within the literature, aerobic exercise has been found to decrease IOP acutely regardless of intensity. In one example IOP decreased 2.43 ± 0.30 mmHg after walking, 3.85 ± 0.55 mmHg after jogging, and 4.0 ± 0.37 mmHg after running.¹⁴ Resistance training, whether isotonic or isometric, may have the opposite effect. IOP increased in subjects after performing isometric squats and a 2.9 mmHg increase after performing 4 sets of bench press at 95% 1RM.^15,16,44 These findings contrast with the work of Risner et al. which found that acute and transient decreases in IOP with isometric and dynamic exercise were more pronounced in patients with glaucoma.⁴³

Aerobic exercise has also been shown to decrease IOP in the long-term. A 3-month aerobic exercise program found IOP to be lower than their original baseline over a 24-h period after they participated.³⁰ Resistance training may also cause a long-term decrease in IOP, as subjects’ baseline IOP decreased by 2.18 ± 2.25 after participating in a 6-week exercise program.²¹ However, this may not be attributable to resistance training as the program also included aerobic exercise which has already been shown to lower IOP long-term.²¹

Both aerobic exercise and resistance training have been shown to increase BP acutely as subjects’ SBP and DBP went up by an average of 8.6 mmHg and 7.33 mmHg, respectively, 5 min after exercising.⁴⁸ This is in line with the reasoning that more blood needs to be pumped to muscles during exercise as a result of an increased oxygen requirement.⁵⁰ Engaging in a long-term exercise program, however, has been shown to have the opposite effect whether one partakes in aerobic exercise, isometric exercise, or isotonic exercise. This was confirmed by a study in which multiple subjects were placed in groups that performed aerobic, isometric, or isotonic exercises over 4 weeks.²⁰ The isotonic group experienced an SBP and DBP decrease of 1.8 ± 1.8 mmHg and 3.2 ± 1.2 mmHg while the isometric group experienced an SBP and DBP decrease of 0.9 ± 3.5 mmHg and 6.2 ± 4.2 mmHg, respectively. The group that performed aerobic exercise experienced an SBP and DBP decrease of 3.5 ± 1.2 mmHg and 2.5 ± 0.8 mmHg, respectively.²⁰

Exercise has also been shown to increase OPP acutely which is consistent with the findings that exercise produces an acute increase in BP. Isometric exercise acutely raised OPP by 6.27 ± 1.15 mmHg in men and 7.36 ± 1.61 mmHg in women.⁵⁴ In most parts of the eye, this will not cause an acute raise in OBF due to vascular autoregulation; however, autoregulation is weaker in the choroid, so exercise may be able to increase the circulation.^33,44 Pilot evidence suggests autoregulation can fail if a subject’s OPP reaches 67% above baseline, however, but this is only a short-term effect that will not occur over a long-period of time.³³

Finally, acute and chronic forms of exercise and their effects on POAG risk include connections to neuroprotection and mental health. Upregulation of brain-derived neurotrophic factor and enhancement of mitochondrial function might be effective in preventing vision loss caused by retinal ganglion cell death.⁴⁴ Additionally, anxiety and depression, common among patients with glaucoma, can be potentially alleviated with physical exercise.⁴⁴ These effects may improve patient quality of life beyond protecting against the onset and progression of POAG itself.

Summary

The paradigm of exercise and its benefits to human health is universally understood, however the impact of different forms of physical activity on POAG disease is poorly defined. Population-based studies currently reach different conclusions rather than supporting a common result or specific suggested form of preventative exercise.^6,7,22 Among available data, acute and chronic forms of exercise differently alter glaucoma risk by impacting several risk factors for glaucoma, including IOP, BP, OPP, and OBF. Different types and duration of exercise significantly alter many physiological processes including fluid balance, cellular (i.e., mitochondrial) function and stress response, and metabolism, yet consensus on the long-term effects of any exercise program on POAG disease is currently missing.

Evidence suggests aerobic forms of exercise decreases IOP both acutely and long-term, while resistance training increases IOP acutely but reduces it long-term.^14,15,21 All exercise, whether aerobic, isotonic, or isometric acutely increases BP, but decreases BP in the long-term.⁴⁸ Both aerobic exercise and resistance training acutely increase OPP, but the effect on OBF may be negligible because of vascular autoregulation.^33,44 While the choroid has little to no autoregulation, allowing for pass-through increases in blood flow after exercise, other areas like the retina have strong autoregulation which makes it more difficult for exercise to increase OBF.^33,44 The ONH is affected by both the choroidal and retinal circulations, making the net effect of exercise on OBF to the ONH difficult to assess. A healthy vascular regulatory ability is likely a key factor in maintaining appropriate IOP and ocular perfusion during exercise routines. Pathologically altered autoregulatory abilities may elevate POAG risk both during and following acute and chronic exercise programs when compared to healthy individuals.

This review has several limitations. First, the studies included are diverse in goals and were not designed with exercise as the primary aim of study. Second, data from current studies do not encompass all age and racial groups, further limiting the generalizability of the information across populations. In addition, what may be considered high-intensity exercise in one study might be only considered moderate-intensity exercise in another study. It is also unclear whether the results of studies examining the effect of regular high-intensity exercise can be generalized to individuals who engage in intermittent, lower-intensity physical activity. The topic of exercise across a person’s lifespan is inherently complex, and most currently available data involve inferred risk factors and not direct outcomes of exercise to glaucoma. While aerobic exercise may lower IOP over time, due to the limitations of the diverse literature, a careful interpretation of all results is suggested in terms of impact on glaucoma.

Protective mechanisms of action for exercise related to POAG include decreased blood pH, hyperosmolarity, elevated blood lactate, NO and NO metabolites, ET-1 (not ET-2), and elevated antioxidants that improve metabolism, cellular response, and a reduction in reactive oxygen species (ROS). Overall, exercise may need to be aerobic and/or dynamic and followed over an extended period to lower the risk of glaucoma. Dynamic, long-term exercise significantly lowers IOP and BP, but IOP may return to baseline after ending exercise programs. Isometric exercise (including breath-holding or the head-down position) and heavy weight use should be avoided in high-risk patients because these may acutely elevate IOP. Data indicates that physical exercise consistently improves OPP, but the effect on ocular circulation may be dampened by functioning autoregulation in healthy subjects. In addition to its influence on POAG risk factors, exercise may be neuroprotective and may reduce anxiety and depression associated with glaucoma. As the most significant limitation is non-uniformity of data, along with carefully designed trials, the use of artificial intelligence (AI) may help reveal the exact influence of different forms of exercise on POAG. Future studies should seek to isolate various forms and duration of activities accounting for acute, chronic, aerobic and anerobic training, and focus on identifying exercise’s long-term influence on POAG disease progression.