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The Optic Nerve Head Perfusion Equation: Venous Pressure, IOP, and Susceptibility to Damage · Glaucoma, Vision & Longevity: Supplements & Science

• 0:00
  SPEAKER_00: The optic nerve head perfusion equation, balancing arterial and venous pressures.
• 0:06
  SPEAKER_00: Glaucoma, optic nerve damage, has long been linked to high intraocular pressure, IOP, but doctors now recognize that blood flow through the eye is just as important to optic nerve health.
• 0:17
  SPEAKER_00: In the eye, blood enters through arteries carrying a high pressure from the heart and must exit through veins carrying lower pressure.
• 0:25
  SPEAKER_00: The perfusion pressure that drives blood through the optic nerve head, ONH, where the nerve fibers exit the eye, depends on the difference between these pressures, but with a twist.
• 0:35
  SPEAKER_00: Unusually, the eyeball's pressure, IOP, physically squeezes the veins leaving the eye, the vortex and episclal veins, so that these veins must have pressures just above IOP to stay open.
• 0:47
  SPEAKER_00: In other words, ocular veins behave like a starling resistor.
• 0:51
  SPEAKER_00: Their outflow pressure is kept near IOP to prevent collapse.
• 0:55
  SPEAKER_00: This means eye perfusion pressure is often approximated as arterial pressure minus IOP.
• 1:00
  SPEAKER_00: In practice, doctors often estimate ocular perfusion pressure by subtracting IOP from mean arterial pressure, roughly through blood pressure.
• 1:10
  SPEAKER_00: However, this is only an approximation.
• 1:12
  SPEAKER_00: Actual venous pressure can deviate from IOP, especially at low IOPs, which makes true perfusion pressure lower than the formula predicts.
• 1:21
  SPEAKER_00: In one eye model, researchers found choroidal venous pressure stayed higher than IOP, so real perfusion might be overestimated by the simple formula.
• 1:30
  SPEAKER_00: In addition to IOP acting from inside the eye, the optic nerve head lamina cribrosa, the sieve-like tissue at the back of the eye, is also pressed on by the pressure in the subraspinal fluid, CSF, around the optic nerve.
• 1:44
  SPEAKER_00: Normally CSF pressure, essentially intracranial pressure, is somewhat lower than IOP, so the lamina sees a net gradient pushing it backwards.
• 1:53
  SPEAKER_00: This translaminar pressure difference, IOP minus CSF pressure, causes posterior bowing of the lamina.
• 2:00
  SPEAKER_00: When it is large, nerve fibers and blood vessels in the lamina can be strained.
• 2:04
  SPEAKER_00: For example, if IOP is 20 mm horgrams and CSF pressure is 10 millimeter hoggrams, the lamina experiences about a 10 mm difference.
• 2:13
  SPEAKER_00: Since the lamina is only a few hundred micrometers thick, that works out to roughly 1 mm of gradient per 100 micrometers of tissue, one of the steepest pressure gradients in the body.
• 2:24
  SPEAKER_00: Animal and human studies suggest that this translaminar gradient itself can damage the optic nerve.
• 2:30
  SPEAKER_00: In fact, modern research shows that a low CSF pressure, leading to a high IOP CSF difference, can be as damaging to the optic nerve head as a high IOP.
• 2:40
  SPEAKER_00: In normal pressure glaucoma patients, IOP 21 mmHg, low blood pressure or especially low CSF pressure can excessively increase this gradient, starving the lamina of blood flow.
• 2:53
  SPEAKER_00: How arteries and veins drive ONH perfusion.
• 2:56
  SPEAKER_00: As in any tissue, arterial blood pressure pushes blood into the eye's circulation, and resistance in the tiny vessels reduces pressure by the time blood reaches the veins.
• 3:06
  SPEAKER_00: Normally this sets up a downward pressure gradient from arteries to veins, but in the eye, the external pressure of IOP compresses the outflow veins, forcing the vein pressure to stay just above IOP.
• 3:17
  SPEAKER_00: In practice, this means blood must overcome the sum of IOP and any venous pressure to reach the tissues of the ONH.
• 3:25
  SPEAKER_00: In simple terms, ocular perfusion pressure is often taken as arterial pressure minus IOP, assuming venous pressure IOP.
• 3:33
  SPEAKER_00: This approximation highlights two key factors for flow, arterial pressure, linked to heart blood pressure, and IOP.
• 3:41
  SPEAKER_00: If blood pressure drops, for example, at night or IOP spikes, perfusion can fall.
• 3:46
  SPEAKER_00: Indeed, wide swings in IOP or blood pressure are risk factors for glaucoma damage.
• 3:51
  SPEAKER_00: Recent work confirms that large fluctuations in calculated OPP, blood pressure minus IOP, are linked to progression of normal tension glaucoma.
• 4:00
  SPEAKER_00: For instance, one trial found that although both latanoprost and bimatoprost lowered IOP equally, only latanoprost significantly raised the eye's calculated perfusion pressure, likely through modest effects on blood flow.
• 4:14
  SPEAKER_00: Importantly, the above formula neglects direct venous pressure terms.
• 4:19
  SPEAKER_00: In reality, if venous pressure is elevated, for example by raised intracranial pressure, or conditions like heart failure or obstructive breathing that raise thoracic pressures, perfusion pressure is reduced.
• 4:31
  SPEAKER_00: Research in animal eyes shows that at low IOPs, venous pressure can actually exceed IOP, causing actual perfusion pressure, arterial minus venous, to be less than the simple MAP IOP estimate.
• 4:44
  SPEAKER_00: In glaucoma patients, higher episcoral venous pressure, EVP, has been observed with some treatments, blunting pressure reduction.
• 4:51
  SPEAKER_00: In one animal model, experimentally raising venous pressure dramatically lowered ONH perfusion.
• 4:57
  SPEAKER_00: Altogether, narrowing or congestion of the ocular veins lowers the overall pressure gradient that drives blood through the optic nerve, making the nerve tissue more susceptible to damage even if IOP is not very high.
• 5:11
  SPEAKER_00: Imaging and blood flow studies in glaucoma.
• 5:13
  SPEAKER_00: Modern imaging and blood flow measurements confirm that glaucoma eyes often suffer from poor optic nerve perfusion.
• 5:21
  SPEAKER_00: Optical coherence tomography angiography, OCTA, shows that glaucoma is associated with loss of capillaries.
• 5:28
  SPEAKER_00: Vessel density in the retina, around the nerve, and in the peripapillary choroid is significantly lower in glaucoma patients.
• 5:36
  SPEAKER_00: These microvascular defects correlate closely with nerve fiber loss and visual field defects, suggesting a link between poor blood supply and nerve damage.
• 5:45
  SPEAKER_00: In one OCT study, the overall optic disc flow index, a measure of blood flow, was about 25% lower in glaucoma eyes than in normals, even after accounting for scan variability.
• 5:57
  SPEAKER_00: Hemodynamic imaging adds to this picture.
• 6:01
  SPEAKER_00: Color Doppler ultrasound studies show that blood velocities in the eyes feeding arteries, ophthalmic, central retinal, and short posterior ciliary arteries, are lower in both high tension and normal tension glaucoma than in healthy eyes.
• 6:15
  SPEAKER_00: Laser-based flometry assays similarly record reduced blood flow on the surface of the optic nerve head in glaucoma.
• 6:22
  SPEAKER_00: For example, laser Doppler velocimetry finds less blood in the small capillaries nourishing the nerve fiber layer of glaucoma eyes.
• 6:31
  SPEAKER_00: Scanning laser flometry in the nerve head cup and rim also consistently shows lower microvascular perfusion in glaucoma patients than in healthy or ocular hypertension subjects.
• 6:42
  SPEAKER_00: Notably, these reductions in flow correlate with the extent of nerve damage.
• 6:47
  SPEAKER_00: More severe glaucoma tends to coincide with greater loss of ONH perfusion.
• 6:52
  SPEAKER_00: Other techniques have similar findings.
• 6:55
  SPEAKER_00: Laser speckle flography studies indicate that even at the earliest stages of glaucoma, the optic nerve head blood flow can initially rise, possibly from loss of autoregulation, and then steadily declines as damage progresses.
• 7:09
  SPEAKER_00: By the time a large fraction of the nerve fiber layer is lost, ONH blood flow can be 25% below baseline.
• 7:17
  SPEAKER_00: Long-term studies also suggest that eyes with poorer baseline perfusion, for example due to higher vascular resistance, are more likely to go on to lose visual field faster.
• 7:27
  SPEAKER_00: For instance, in a three-year study of treated glaucoma patients, those who progressed showed higher resistivity, lower flow, in the ophthalmic and ciliary arteries at baseline.
• 7:38
  SPEAKER_00: Together, these imaging and blood flow data show a clear pattern.
• 7:42
  SPEAKER_00: Glaucoma optic nerves often have less blood flow and perfusion than normal.
• 7:47
  SPEAKER_00: While this is partly a consequence of IOP-related compression, a narrowed pressure gradient, it also implies that any additional factor that reduces flow, such as venous congestion or low arterial pressure, can compound the problem.
• 8:02
  SPEAKER_00: Therapeutic approaches, beyond just lowering IOP.
• 8:06
  SPEAKER_00: Because glaucoma damage can happen even at normal IOP, researchers emphasize treatments that also protect or improve optic nerve blood flow.
• 8:14
  SPEAKER_00: Lowering IOP remains first line, but supplemental strategies target the vascular side.
• 8:19
  SPEAKER_00: Some glaucoma drugs have beneficial blood flow effects.
• 8:23
  SPEAKER_00: For example, the alpha-2 agonist bromonidine not only lowers IOP, it also improves retinal and ONH circulation.
• 8:30
  SPEAKER_00: Although bromonidine constricts some vessels on the eye's surface, it paradoxically dilates retinal arterioles and increases overall ocular blood flow.
• 8:39
  SPEAKER_00: Clinically, in one trial of normal tension glaucoma, patients on bromonidine lost visual field more slowly than those on timolol, even though their IOPs were the same, suggesting the improved perfusion provided some protection.
• 8:53
  SPEAKER_00: Prostaglandin analogues, first-line IOP drugs, may also affect perfusion.
• 8:58
  SPEAKER_00: Laboratory studies found that latanoprost enhanced optic nerve blood circulation in animals and humans independently of its IOP effect.
• 9:07
  SPEAKER_00: In a clinical trial comparing latanopost with bimatoprost, both drugs lowered IOP equally, but only latanoprost increased calculated ocular perfusion pressure.
• 9:18
  SPEAKER_00: It appears that some medications can also change the downstream venous pressure.
• 9:22
  SPEAKER_00: For example, topical prostaglandins were found to raise episcoral venous pressure in animals, partially offsetting their benefit.
• 9:30
  SPEAKER_00: New approaches are looking to target venous pressure more directly.
• 9:34
  SPEAKER_00: One experimental drug, a chromacylim pro drug, successfully lowered episcleral venous pressure in mice and thereby reduced IOP, demonstrating that veins can be an active drug target.
• 9:46
  SPEAKER_00: Carbonic anhydrase inhibitors, another class of glaucoma drops, have a vasodilating side effect.
• 9:53
  SPEAKER_00: By altering pH, CAIs tend to dilate blood vessels and improve retinal perfusion.
• 9:59
  SPEAKER_00: In animal glaucoma models, dorzolamide, a CAI, reduced nerve cell loss as much as timolol did, and this protective effect was attributed largely to its IOP lowering, but the vasodilation likely also helped oxygenate the nerve.
• 10:12
  SPEAKER_00: Beyond existing medications, novel neuroprotective or vasoactive agents are under study.
• 10:18
  SPEAKER_00: Rochinase rock inhibitors, a newer class of eyedrops, have been shown to increase optic nerve blood flow in animal studies.
• 10:26
  SPEAKER_00: Even dietary supplements like ginkgo boloba have drawn attention.
• 10:30
  SPEAKER_00: It has antioxidant and vessel widening effects, and in a small trial it lowered levels of endothelin-1, a vasoconstrictor, in glaucoma patients, suggesting improved blood flow to the optic nerve.
• 10:42
  SPEAKER_00: Other treatments focus on systemic factors, for instance, ensuring a patient's blood pressure stays at a healthy level, avoiding nighttime dips, can help maintain ocular perfusion in normal tension glaucoma.
• 10:56
  SPEAKER_00: In short, modern glaucoma care is moving toward a two-equation approach, not only reducing IOP, but also optimizing the pressure gradient that drives blood flow through the optic nerve.
• 11:08
  SPEAKER_00: This means considering arterial blood pressure, lowering any unnecessary venous backup, and potentially using drugs that boost microvascular perfusion or protect nerves from ischemia.
• 11:19
  SPEAKER_00: By treating the optic nerve's blood supply as well as mechanical pressure, doctors hope to slow glaucoma damage even when IOP alone cannot be lowered further.
• 11:29
  SPEAKER_00: Conclusion.
• 11:30
  SPEAKER_00: The health of the optic nerve head depends on a fine balance between IOP, arterial supply, and venous outflow.
• 11:37
  SPEAKER_00: Higher venous or CSF pressure or lower arterial pressure all reduce the perfusion pressure across the lamina crybrosa, starving nerve fibers of blood.
• 11:47
  SPEAKER_00: Clinical imaging and flow studies confirm that glaucoma eyes often have compromised blood flow, thinner capillary networks, slower flow velocities, which correlates with nerve loss.
• 11:57
  SPEAKER_00: Effective glaucoma management thus includes both IOP reduction and measures to improve or protect blood flow.
• 12:04
  SPEAKER_00: Future therapies may directly target improving ocular perfusion, for example, via vasodilation or lowering venous pressure, in addition to the traditional goal of lowering IOP.
• 12:15
  SPEAKER_00: Sources key findings in this review are supported by studies of ocular blood flow and glaucoma.
• 12:21
  SPEAKER_00: For example, recent OCT angiography studies document lower optic nerve vessel density in glaucoma eyes.
• 12:29
  SPEAKER_00: Foundational work on the translaminar pressure gradient is described by Chowdery et al.
• 12:34
  SPEAKER_00: The influence of IOP and venous pressure on perfusion, the Starling resistor model, is reviewed in Boltz et al.
• 12:42
  SPEAKER_00: Clinical trials and experiments on glaucoma medications note their vascular effects, e.g., bromonidine's blood flow increase, latanoprost improving perfusion, CAIs inducing vasodilation.
• 12:54
  SPEAKER_00: Doppler and laser flow studies demonstrate reduced ocular blood flow in glaucoma patients.
• 12:59
  SPEAKER_00: These and other peer-reviewed sources have been used to inform this discussion.
• 13:04
  SPEAKER_00: All links to sources are available in the text version of this article.
• 13:08
  SPEAKER_00: You can find the full article at VisualFieldTest.com.
• 13:13
  SPEAKER_00: Thanks for listening.
• 13:14
  SPEAKER_00: To check your visual field, click the link at the bottom of this article or visit visualfieldtest.com.