Intraocular pressure (IOP) is the fluid pressure of the eye. As pressure is a measure of force per area, IOP is a measurement involving the magnitude of the force exerted by the aqueous humor on the internal surface area of the anterior eye. The IOP can be theoretically determined by the Goldmann equation, which is IOP = (F/C) + P, where F represents aqueous flow rate, C represents aqueous outflow, and P is the episcleral venous pressure. A change or fluctuation in any of these variables will inevitably alter the IOP.

Intraocular pressure is carefully regulated, and disturbances are often implicated in the development of pathologies such as glaucoma, uveitis, and retinal detachment. IOP exists as a fine-tuned equilibrium between the production and drainage of aqueous humor. The balance between IOP increases with increased systemic blood pressure. Sudden increases in IOP can cause mechanical stress and ischemic effects on the retinal nerve fiber layer, while sudden decreases in IOP can cause micro-bubbles to form from dissolved gases in microvasculature with resultant gas emboli and ischemic tissue damage.[1] Chronic elevation of IOP has been infamously implicated in the pathogenesis of primary open-angle glaucoma (POAG) and other vision-damaging problems. 

In approaching intraocular pressure, a basic understanding of the production and outflow of the aqueous humor is helpful. Aqueous humor is produced by the ciliary epithelium of the iris ciliary body pars within the posterior chamber of the anterior eye. Aqueous humor accumulates in the posterior chamber and flows through the pupil into the anterior chamber. Aqueous humor then exits the anterior chamber via one of three routes:

1. The vast majority of aqueous humor drains through the trabecular meshwork at the angle of the anterior chamber and into the Schlemm canal where it enters episcleral veins.
2. A small amount of the aqueous humor passes into the suprachoroidal space and enters venous circulation in the ciliary body, choroid, and sclera.
3. A still smaller amount of aqueous humor transits through the iris and back into the posterior chamber.

An intricate and elegant homeostatic mechanism maintains intraocular pressure. Acutely, the sympathetic nervous system directly influences the secretion of aqueous, with beta-2 receptors causing increased secretion and alpha-2 receptors causing decreased secretion. Homeostatic regulation of IOP, however, relies primarily on the regulation of aqueous outflow through the trabecular meshwork. This regulation occurs through modulation of the resistance of the TM outflow tract in the juxtacanalicular region (region bordering SC), likely at the level of the inner wall basement membrane.[2] IOP forces produce mechanical stress of the cells of this layer, which initiates a signal cascade leading to increased activity of matrix metalloproteinases (specifically MMP14 and MMP2) with a resultant increase in cell turnover at the level of the TM, allowing increased aqueous humor outflow.[3]

Intraocular pressure is traditionally measured by applanation tonometry, which gives an estimate of the pressure inside the anterior eye based on the resistance to flattening of a small area of the cornea. Pressures of between 11 and 21 mmHg are considered normal, and diurnal variance of IOP is expected, with higher pressures typically found in the morning. While the mainline modality for measurement of IOP remains Goldmann applanation tonometry (GAT), rebound tonometry using portable tonometers has emerged as a practical measurement of IOP in the acute setting. These two modalities, however, are not exchangeable according to current research.[4] More recently has seen the development of microelectromechanical and nanoelectromechanical systems for 24-hour monitoring of intraocular pressure.[5] While larger studies are required to validate their safety and efficacy, these newer systems will play a large role in the management and monitoring of patients with pressure-related pathology.

Limitations exist in applanation technology due to reliance on the Imbert-Fick principle, which presumes that pressure within a sphere is equal to the force necessary to flatten its surface divided by the area flattened.[6] This principle does not take into account the inherent rigidity or biomechanical properties of the corneal wall. Indeed, it only works in this context because the force of capillary attraction of the tear meniscus opposes corneal rigidity when the flattened area is 3.06 mm in diameter. If, for example, the corneal wall is exceptionally thick, a large force will be required to flatten it; but this force may not correspond to an elevated IOP, resulting in an overestimation of IOP. For this reason, the measurement of central corneal thickness is critical for accurate measurement of IOP.

Homeostasis of intraocular pressure is of vital importance to overall eye health and function. Disruption of this fine balance may have devastating consequences, contributing to the pathogenesis of glaucoma, uveitis, and choroidal detachment.

The definition of ocular hypertension (OHT) is intraocular pressure that is two standard deviations above the mean IOP (16 mmHg) with normal visual fields and no detectable glaucomatous damage.[7] When IOP is high above the normal range, there is an increased incidence of development of primary open-angle glaucoma.

Primary open-angle glaucoma is a chronic degeneration of the optic nerve characterized by the AAO as showing evidence of optic nerve damage from optic disc abnormalities, retinal nerve fiber structure abnormalities, or reproducible visual field defects without other explanations.[8] While the pathogenic relationship between IOP and glaucomatous optic neuropathy is not fully understood, elevated IOP is highly associated with the development of retinal ganglion cell death. Multiple mechanisms are postulated to be the causative link between elevated IOP and the development of glaucoma. The suspicion is that elevated IOP causes direct mechanical damage to the retinal ganglion cell axons. Alternatively, there have been suggestions that the elevated IOP produces a shearing of the dorsal attachments of the astrocytes from the optic nerve head, resulting in a loss of metabolic support to the optic nerve head.[9] Other possible mechanisms include ischemic damage due to compression of blood vessels supplying the optic nerve head. Recently, IOP variance has been noted to occur during the natural sleep cycle. These sleep-related fluctuations may also play a role in the progression of glaucoma, but larger studies are required to uncover its exact role in the pathogenesis of retinal ganglion cell death.[10]

Anterior uveitis, an inflammation of the anterior uveal tract, frequently leads to derangement of intraocular pressure homeostasis. In some cases, inflammation of the pars plicata of the ciliary body can result in the ciliary body to shut down, resulting in IOP that is below the normal range. In other cases, inflammation of the anterior uveal tract disrupts aqueous outflow, resulting in elevated IOP. In this case, prolonged elevation in IOP will result in glaucomatous optic neuropathy (inflammatory glaucoma).[11]

In the setting of decreased intraocular pressure or hypotony, serous choroidal detachment is a distinct danger. Increased transmural pressure secondary to decreased IOP, results in transudation of serum into the suprachoroidal space. The result is a progressive detachment of the retina and choroid.[12]

Elevated intraocular pressure is the crucial modifiable risk factor in the development of primary open-angle glaucoma. Other risk factors for glaucoma include older age, central corneal thickness, cup/disc ratio, and pattern standard deviation. In the clinical setting, a critical relevance of intraocular pressure is its utility for diagnosis and treatment of ocular hypertension before the development of glaucoma. The landmark Ocular Hypertension Treatment Study showed that elevated IOP in the setting of decreased corneal thickness carries a significant risk for the development of glaucoma. It has also been shown that treatment of ocular hypertension in this setting with topical ocular hypotensive medication is effective for delaying or preventing the development of primary open-angle glaucoma.[13]

Despite the proven vision-preserving benefits of early treatment, there remains a dearth of evidence for the benefits of screening for primary open-angle glaucoma in the general population. Even the cutoff of 21 mmHg for reference range IOP has been in dispute in recent years. Many patients with elevated IOP and other associated risk factors never develop visual problems. Recent AAO guidelines illustrate that the results of multiple population-based studies indicate highly variable proportions of patients with elevated IOP who develop glaucoma, suggesting poor predictive value in utilizing a specific IOP cutoff as a measure for screening and diagnosis of primary open-angle glaucoma.[8] Furthermore, the United States Preventive Service Task Force has identified significant harm in the potential overdiagnosis and overtreatment of these patients.[14] The AAO currently recommends comprehensive adult medical eye evaluation screening for glaucoma in all patients above the age of 40.[15]