Ocular blood flow may have role in glaucoma

The number of people anticipated to have glaucoma by the year 2040 is 111.8 million worldwide (Tham et al.). While the number is astoundingly large, it amounts to 3.54% of the population 40 to 80 years old. It is on our shoulders to better identify the patients at risk for glaucoma.

As practitioners, perhaps our most common reference for risk factors is the Ocular Hypertension Treatment Study (OHTS). OHTS not only looked at the efficacy of topical hypotensive medication to delay or prevent the onset of primary open angle glaucoma (POAG) in patients with IOP between 24 mm Hg and 32 mm Hg, but it also analyzed the risk factors for progressing to glaucoma (Gordon et al.). OHTS identified older age, vertical cup-to-disc ratio greater than 0.5, higher IOP, greater Humphrey visual field pattern standard deviation and thinner central corneal measurement to all be baseline factors that predicted increased risk for developing POAG over time.

Justin Schweitzer

We also commonly reference the European Glaucoma Prevention Study (EGPS), which was a parallel study to OHTS and identified similar ocular risk factors for glaucoma as well as cardiovascular disease and high blood pressure as possible risk factors (EGPS Group, et al.).

Vascular insults to the optic nerve head

While increased IOP is a risk factor, it likely is not the sole cause of glaucomatous retinal damage. Only 10% of patients with IOP greater than 22 mm Hg have glaucoma, and up to 50% of patients with glaucoma do not have elevated IOP (Klein et al., Tielsch et al.), pushing us to increase our understanding of other factors.

The role of intracranial pressure (ICP) and its importance in relation to glaucoma continues to be investigated. The optic nerve is exposed to ICP as it is surrounded by cerebrospinal fluid (CSF) in the subarachnoid space immediately posterior to the lamina cribrosa. The lamina cribrosa separates the subarachnoid space from the eye, resulting in two pressurized regions, and the decrease in pressure that occurs across the lamina cribrosa is known as the translaminar pressure difference. If a large disparity exists due to either an elevation in IOP or a reduction in ICP, the imbalance could result in glaucomatous changes or damage.

The role of systemic and localized vascular abnormalities has been heavily investigated, with important findings in relation to glaucoma. The population-based Thessaloniki Eye Study found that patients with diastolic blood pressure less than 90 mm Hg due to antihypertensive treatment were more likely to have increased cupping and decreased rim area of the optic disc (Topouzis et al.). Harris and colleagues use the published literature to show a direct link between vasoprotection and cell death within the eye that characterizes glaucoma, and a 2009 consensus paper points to impaired ocular blood flow as a potential contributing factor to ocular nerve damage (Weinreb et al.).

The Leuven Eye Study further analyzed the link between glaucoma and vascular data and found that higher ocular perfusion pressure, lower retrobulbar blood flow velocity, higher retinal venous saturation and higher choroidal thickness asymmetry all significantly corresponded to glaucoma (Abegao et al.). It has been theorized that impaired vascular autoregulation (the ability of vessels to appropriately dilate/constrict in response to varying blood pressure) leaves the optic nerve head susceptible to ischemic damage from variations in ocular perfusion pressure and IOP, which then further impairs autoregulation in a cyclical fashion and results in the damage to the optic nerve head associated with glaucoma (Moore et al.). While it is not always possible to measure ocular perfusion pressure and other vascular functions in the clinic, a patient’s medical history can reveal other diseases of defective vasoregulation that may be worthy of increased attention. Raynauds phenomenon and migraines are just two examples that have been directly correlated to normal tension glaucoma (Mallick et al., Drance et al.).

Beyond lowering IOP

When a patient presents with high IOP, it is fairly clear what course of action we should take. OHTS showed that glaucoma could be prevented in a meaningful percentage of eyes by lowering IOP. Evidence shows that decreased blood flow is also part of the puzzle of glaucoma, so enhancing ocular blood flow may also be a worthwhile adjunct treatment.

A recently published study by Harris and colleagues investigated the effects of an antioxidant dietary supplement on retinal and retrobulbar blood flow and found that 1 month of oral supplementation produced a statistically significant increase in peak systolic and end diastolic blood flow velocities in all retrobulbar blood vessels examined. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries. In retinal capillary beds surrounding the optic nerve head, significant increases were seen in both mean ocular blood flow velocity and vascular perfusion – indicating a higher proportion of vessels receiving blood.

In the study, 45 study participants with POAG were given the nutritional supplement Optic Nerve Formula (ScienceBased Health) or placebo for 1 month, followed by washout, and switched treatments. The supplement contains essential vitamins and minerals, omega-3 fatty acids, amino acids, dietary polyphenols and botanical extracts from sources such as ginkgo biloba and bilberry. This study adds to previous findings indicating that supplementation with ginkgo or dietary polyphenols can improve ocular blood flow and slow progression of normal-tension glaucoma (Chung et al., Park et al., Ohguro et al., Steigerwalt et al.).

Informing patients

We do not fully understand glaucoma. We know that IOP matters, and we treat that with hypotensive drops or surgery. However, there are other components to glaucoma, and it is important to provide patients with every option to preserve their vision. We already talk to our patients about IOP and how it impacts the ocular nerve; it is the logical next step to discuss blood flow and the role of vascular deficiencies in glaucoma.

The value of nutritional supplementation is gaining appreciation among health care providers and patients; this is evidenced by the Age-Related Eye Disease Study 2 nutritional formula for macular degeneration and the use of omega fatty acids in dry eye disease. The discussion about specific nutrients that can help blood flow should be no different. I see no reason not to at least discuss with every glaucoma patient an additive step they can take that may help them and has no downside. As eye care practitioners, we continue to do everything we can to preserve sight, and this is one more tool that can help patients. – by Justin Schweitzer, OD, FAAO

Disclosure: Schweitzer reports no relevant financial disclosures.

The number of people anticipated to have glaucoma by the year 2040 is 111.8 million worldwide (Tham et al.). While the number is astoundingly large, it amounts to 3.54% of the population 40 to 80 years old. It is on our shoulders to better identify the patients at risk for glaucoma.

As practitioners, perhaps our most common reference for risk factors is the Ocular Hypertension Treatment Study (OHTS). OHTS not only looked at the efficacy of topical hypotensive medication to delay or prevent the onset of primary open angle glaucoma (POAG) in patients with IOP between 24 mm Hg and 32 mm Hg, but it also analyzed the risk factors for progressing to glaucoma (Gordon et al.). OHTS identified older age, vertical cup-to-disc ratio greater than 0.5, higher IOP, greater Humphrey visual field pattern standard deviation and thinner central corneal measurement to all be baseline factors that predicted increased risk for developing POAG over time.

Justin Schweitzer

We also commonly reference the European Glaucoma Prevention Study (EGPS), which was a parallel study to OHTS and identified similar ocular risk factors for glaucoma as well as cardiovascular disease and high blood pressure as possible risk factors (EGPS Group, et al.).

Vascular insults to the optic nerve head

While increased IOP is a risk factor, it likely is not the sole cause of glaucomatous retinal damage. Only 10% of patients with IOP greater than 22 mm Hg have glaucoma, and up to 50% of patients with glaucoma do not have elevated IOP (Klein et al., Tielsch et al.), pushing us to increase our understanding of other factors.

The role of intracranial pressure (ICP) and its importance in relation to glaucoma continues to be investigated. The optic nerve is exposed to ICP as it is surrounded by cerebrospinal fluid (CSF) in the subarachnoid space immediately posterior to the lamina cribrosa. The lamina cribrosa separates the subarachnoid space from the eye, resulting in two pressurized regions, and the decrease in pressure that occurs across the lamina cribrosa is known as the translaminar pressure difference. If a large disparity exists due to either an elevation in IOP or a reduction in ICP, the imbalance could result in glaucomatous changes or damage.

The role of systemic and localized vascular abnormalities has been heavily investigated, with important findings in relation to glaucoma. The population-based Thessaloniki Eye Study found that patients with diastolic blood pressure less than 90 mm Hg due to antihypertensive treatment were more likely to have increased cupping and decreased rim area of the optic disc (Topouzis et al.). Harris and colleagues use the published literature to show a direct link between vasoprotection and cell death within the eye that characterizes glaucoma, and a 2009 consensus paper points to impaired ocular blood flow as a potential contributing factor to ocular nerve damage (Weinreb et al.).

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The Leuven Eye Study further analyzed the link between glaucoma and vascular data and found that higher ocular perfusion pressure, lower retrobulbar blood flow velocity, higher retinal venous saturation and higher choroidal thickness asymmetry all significantly corresponded to glaucoma (Abegao et al.). It has been theorized that impaired vascular autoregulation (the ability of vessels to appropriately dilate/constrict in response to varying blood pressure) leaves the optic nerve head susceptible to ischemic damage from variations in ocular perfusion pressure and IOP, which then further impairs autoregulation in a cyclical fashion and results in the damage to the optic nerve head associated with glaucoma (Moore et al.). While it is not always possible to measure ocular perfusion pressure and other vascular functions in the clinic, a patient’s medical history can reveal other diseases of defective vasoregulation that may be worthy of increased attention. Raynauds phenomenon and migraines are just two examples that have been directly correlated to normal tension glaucoma (Mallick et al., Drance et al.).

Beyond lowering IOP

When a patient presents with high IOP, it is fairly clear what course of action we should take. OHTS showed that glaucoma could be prevented in a meaningful percentage of eyes by lowering IOP. Evidence shows that decreased blood flow is also part of the puzzle of glaucoma, so enhancing ocular blood flow may also be a worthwhile adjunct treatment.

A recently published study by Harris and colleagues investigated the effects of an antioxidant dietary supplement on retinal and retrobulbar blood flow and found that 1 month of oral supplementation produced a statistically significant increase in peak systolic and end diastolic blood flow velocities in all retrobulbar blood vessels examined. Vascular resistance was also reduced in central retinal and nasal short posterior ciliary arteries. In retinal capillary beds surrounding the optic nerve head, significant increases were seen in both mean ocular blood flow velocity and vascular perfusion – indicating a higher proportion of vessels receiving blood.

In the study, 45 study participants with POAG were given the nutritional supplement Optic Nerve Formula (ScienceBased Health) or placebo for 1 month, followed by washout, and switched treatments. The supplement contains essential vitamins and minerals, omega-3 fatty acids, amino acids, dietary polyphenols and botanical extracts from sources such as ginkgo biloba and bilberry. This study adds to previous findings indicating that supplementation with ginkgo or dietary polyphenols can improve ocular blood flow and slow progression of normal-tension glaucoma (Chung et al., Park et al., Ohguro et al., Steigerwalt et al.).

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Informing patients

We do not fully understand glaucoma. We know that IOP matters, and we treat that with hypotensive drops or surgery. However, there are other components to glaucoma, and it is important to provide patients with every option to preserve their vision. We already talk to our patients about IOP and how it impacts the ocular nerve; it is the logical next step to discuss blood flow and the role of vascular deficiencies in glaucoma.

The value of nutritional supplementation is gaining appreciation among health care providers and patients; this is evidenced by the Age-Related Eye Disease Study 2 nutritional formula for macular degeneration and the use of omega fatty acids in dry eye disease. The discussion about specific nutrients that can help blood flow should be no different. I see no reason not to at least discuss with every glaucoma patient an additive step they can take that may help them and has no downside. As eye care practitioners, we continue to do everything we can to preserve sight, and this is one more tool that can help patients. – by Justin Schweitzer, OD, FAAO

Disclosure: Schweitzer reports no relevant financial disclosures.