Ocular Hypertension

Updated: Mar 16, 2020
Author: Anne Chang-Godinich, MD, FACS; Chief Editor: Hampton Roy, Sr, MD 



Ocular hypertension (OHT) can be used as a generic term referring to any situation in which intraocular pressure (IOP) is greater than 21 mm Hg, the widely accepted upper limit of normal intraocular pressure in the general population. (See the image below.) The term makes no mention of whether or not glaucomatous nerve damage is present. It also depicts no particular time frame during which the elevated pressure has been measured.

Diagram of intraocular pressure distribution. Used Diagram of intraocular pressure distribution. Used with permission from Survey of Ophthalmology.

The formal definition of ocular hypertension evolved in the latter part of the 20th century.[1] It was used as early as 1962 by Drance, but was not defined in English language publications until 1966 by Perkins and others.

Ocular hypertension is a condition in which the following criteria are met:

  • An intraocular pressure greater than 21 mm Hg in one or both eyes, as measured by applanation tonometry on 2 or more occasions

  • Absence of glaucomatous defects on visual-field testing

  • Normal appearance of the optic disc and nerve fiber layer

  • Anatomically normal, open angles on gonioscopy

  • Absence of ocular conditions contributing to the elevation of pressure, such as narrow angles, neovascular conditions, and uveitis

Despite early definitions, ocular hypertension has historically meant different things to different ophthalmologists.[1] Some glaucoma experts such as Hitchings stressed the point of not reading too much into the term.[2] Others, including Spaeth, advocated total disuse of the term secondary to its inherent ambiguity, preferring the term glaucoma suspect to more adequately convey uncertainty regarding the diagnosis and prognosis.[3] (See the image below.)

Diagram showing the relative proportion of people Diagram showing the relative proportion of people in the general population who have elevated pressure (horizontally shaded lines) and/or damage from glaucoma (vertically shaded lines). Notice that most have elevated pressure but no sign of damage (ie, ocular hypertensives), but there are those with normal pressures who still have damage from glaucoma (ie, normal tension glaucoma). (Diagram used by permission of M. Bruce Shields.) OHT = horizontal lines only NTG = vertical lines only POAG and other glaucomas with both elevated intraocular pressure and damage = overlapping horizontal and vertical lines

The Ocular Hypertension Treatment Study (OHTS) is a multicenter, prospective, randomized, controlled clinical trial studying more than 1800 research subjects, evaluating the safety and efficacy of medical treatment in preventing or delaying the onset of visual-field loss and/or optic nerve damage in patients with ocular hypertension who are at moderate risk for developing primary open-angle glaucoma (POAG).[4]

In this article, ocular hypertension refers to a state in which the eye(s) meet the above 5 criteria, in the absence of identifiable causes or cardinal signs of POAG.[5] Ocular hypertension is a condition requiring closer observation for the potential development of glaucomatous damage.[6, 7]


The exact pathophysiology of elevated intraocular pressure (IOP) in ocular hypertension is not known. In primary open-angle glaucoma, myocilin (MYOC) gene mutations have been found and determined to cause protein misfolding, making trabecular meshwork cells dysfunctional, with subsequent decrease in outflow facility and marked elevation of IOP.[8]

Elevated IOP is of great concern because it is the most established risk factor for the development of glaucoma.[9] Two theories of how IOP initiates glaucomatous damage include (1) onset of vascular dysfunction causing ischemia to the optic nerve and (2) mechanical dysfunction via cribriform plate compression of the neuronal axons.

In addition to vascular compromise and mechanically impaired axoplasmic flow, contemporary hypotheses of possible pathogenic mechanisms that underlie glaucomatous optic neuropathy include excitotoxic damage from excessive retinal glutamate, deprivation of neuronal growth factors, peroxynitrite toxicity from increased nitric oxide synthase activity, immune-mediated nerve damage, and oxidative stress.[10, 11]

The exact role that IOP plays in combination with these other factors and its significance in the initiation and progression of subsequent glaucomatous neuronal damage and cell death over time is still under debate.[12]



Population studies such as the Framingham, Beaver Dam, Baltimore, Rotterdam, Barbados, and Egna-Neumarkt studies have estimated that 4-10% of the population older than 40 years will have IOPs of 21 mm Hg or higher without detectable signs of glaucomatous damage.[13] Ocular hypertension has a 10-15 times greater prevalence than POAG.[14]

Race-related demographics

Although black individuals are considered to have a 3-4 times higher prevalence of POAG and larger cup-to-disc ratios compared with white individuals, the data are less clear concerning ocular hypertension. The Barbados Eye Study found the incidence of IOPs greater than 22 mm Hg to be 5 times higher in blacks than in whites.[13] The Baltimore Eye Survey found no difference in mean IOP between blacks and whites.[15] The Los Angeles Latino Eye Study found Latinos to be at higher risk of ocular hypertension than non-Latino whites but lower than blacks.[16]

Sex-related demographics

The Barbados Eye Study found ocular hypertension present more frequently in women.[13]

Age-related demographics

Mean IOP slowly rises with increasing age. Age older than 40 years is considered a risk factor for the development of ocular hypertension and POAG.[13]


Prospective studies in the 1980s showed that among patients with elevated IOP, roughly 0.5-1% per year developed glaucoma over a period of 5-10 years.[17] The OHTS suggests that progression to glaucoma increases with higher IOPs and lower central corneal thickness (CCT)[4] (see image below) and that certain patient characteristics are associated with a greater than 2% annual risk of developing glaucoma.[18] Patient characteristics associated with this increased risk include the following:

  • Central corneal thickness of less than 555 μm - Annual risk of 3.4%

  • Vertical cup-to-disk ratio of greater than 0.30 - Annual risk of 2.5%

  • African American race - Annual risk of greater than 2%

    Ocular hypertension study (OHTS). Percentage of pa Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness (CCT).

Morbidity and mortality

The Gutenberg Health Study found positive associations with higher IOP in an adult European cohort for systemic cardiovascular risk factors such as hypertension, diabetes, smoking, and obesity.[19]

Systemic morbidity and mortality can also result from the possible cardiopulmonary adverse effects of IOP-lowering medications.

With regard to ocular morbidity and mortality, retinal vascular occlusion may occur in approximately 3% of ocular hypertensive patients.[20]

Progression to glaucoma is the main source of ocular morbidity and mortality. Studies have shown that over a 5-year-period, the incidence of glaucomatous damage in ocular hypertensive patients increases with increasing IOP levels:

  • IOP of 21-25 mm Hg - Approximately 2.6-3%

  • IOP of 26-30 mm Hg - Range from 12-26%

  • IOP higher than 30 mm Hg - Approximately 42%

The Ocular Hypertension Treatment Study (OHTS) states that over a 5-year-period, patients with ocular hypertension and IOP levels of 24 mm Hg or more have a 10% overall risk of developing glaucoma. This risk can be cut in half by medical treatment. In 2004, more than 2 million individuals in the United States were diagnosed as having open-angle glaucoma. This number is projected to increase to more than 3 million by 2020.[21]

Patient Education

Patient education is essential to prevent possible progression to glaucoma. The patient who understands the chronic, potentially progressive nature of glaucoma is more likely to comply with therapy.[22, 23] Numerous handouts are available to patients, including the following:

  • "Understanding and Living with Glaucoma: A Reference Guide for People with Glaucoma and Their Families," Glaucoma Research Foundation, 1-800-826-6693

  • "Glaucoma Patient Resource: Living More Comfortably with Glaucoma," Prevent Blindness America, 1-800-331-2020

For patient education information, see the Eye and Vision Center, as well as Ocular Hypertension and Normal-Tension Glaucoma.




In the evaluation of ocular hypertension, details should be obtained with respect to the following:

  • Past ocular history - History of eye pain or redness; multicolored halos; headache; previous ocular disease, including cataracts, uveitis, diabetic retinopathy, and vascular occlusions; previous ocular surgery, including photocoagulation or refractive procedures; or ocular/head trauma[24]

  • Past medical history - Any surgeries or pertinent vascular illnesses, such as cardiovascular disease, diabetes mellitus, migraine headache, hypertension, and vasospasm[25]

  • Current medications - Hypertensive medications (which may indirectly cause fluctuation of IOP) or topical/systemic corticosteroids[26]

  • Known risk factors for glaucomatous optic neuropathy (POAG) should also be assessed, such as personal history of elevated IOP, advanced age (>50 y), African American descent, myopia, and positive family history/severity of glaucoma in a first-degree relative[27]

Physical Examination

A comprehensive eye examination, such as that outlined in the American Academy of Ophthalmology (AAO) Preferred Practice Patterns, should be performed.[28] Emphasis should be on ruling out early POAG or secondary causes of glaucoma.[29] See the image below.

Flowchart for evaluation of a patient with suspect Flowchart for evaluation of a patient with suspected glaucoma. Used by permission of the American Academy of Ophthalmology.

Visual acuity should be assessed. In isolated ocular hypertension, vision remains normal.

Pupils should be assessed. Afferent pupillary defect (Marcus-Gunn) status should be determined. Ideally, pupil size should be documented at the time of visual-field testing since miosis may mimic early visual-field loss.

Slit-lamp examination of the anterior segment

With regard to the cornea, signs of microcystic edema can be found with a sudden elevation of IOP. Keratic precipitates, pigment on the endothelium (Krukenberg spindle), and congenital and other anomalies suggest a secondary cause of elevated IOP.

For the anterior chamber, assess for an absence of cell or flare, hyphema, foreign bodies, and angle closure.

For the iris, assess for an absence of transillumination defects, iris atrophy, synechiae, rubeosis, ectropion uveae, iris bombé, difference in iris coloration bilaterally (eg, Fuchs heterochromic iridocyclitis), or pseudoexfoliation (PXF) material.

For the lens, assess for an absence of phacomorphic, PXF, Morgagnian, or phacolytic cataract.


Gonioscopy should be performed to rule out angle closure or secondary causes of IOP elevation, such as angle recession, pigmentary glaucoma, or PXF.

Fundus examination

Stereoscopic examination of the optic nerves should be performed, looking for the following possible signs of glaucomatous damage[30] :

  • Enlarged cup-to-disc ratio in the horizontal and vertical meridians

  • Progressive enlargement of the cup

  • Evidence of nerve fiber layer damage with red-free filter

  • Notching or thinning of the disc rim, particularly at the superior and inferior poles

  • Pallor

  • Presence of hemorrhage, most common inferotemporally

  • Asymmetry of cup-to-disc ratio between eyes

  • Peripapillary atrophy

Note the images below.

Illustration of progressive optic nerve damage. No Illustration of progressive optic nerve damage. Notice the deepening (saucerization) along the neural rim, along with notching and increased excavation/sloping of the optic nerve and circumlinear vessel inferiorly. Courtesy of M. Bruce Shields.
Example of optic nerve asymmetry in a patient with Example of optic nerve asymmetry in a patient with glaucomatous damage, left eye, showing optic nerve excavation inferiorly similar to Image 5. Used by permission of M. Bruce Shields.
Glaucomatous optic nerve damage, with sloping and Glaucomatous optic nerve damage, with sloping and nerve fiber layer rim hemorrhage at the 7-o'clock position. Hemorrhage is indicative of progressive damage, usually due to inadequate pressure control. Further notching and pallor corresponding to the area of hemorrhage usually is seen several weeks after resorption of the blood. Courtesy of M. Bruce Shields.
Advanced glaucomatous damage with increased cuppin Advanced glaucomatous damage with increased cupping and substantial pallor of the optic nerve head. Courtesy of M. Bruce Shields.

Other fundus abnormalities that could account for any nonglaucomatous visual-field defects or vision loss (eg, disc drusen, optic pits, macular disease, retinopathy) should be noted.


When checking IOP, record measurements for both eyes, the method used (eg, Goldmann applanation, Tono-Pen, pneumotonometer), and the time the measurement was taken.

Considerations in assessing tonometry measurements are as follows:

  • Is the reading reproducible?

  • What method was used to obtain the reading?

  • What was the time of day?

  • Do both eyes have similar measurements?

  • Is the tonometry value adjusted for corneal pachymetry?

In patients who are obese or anxious, consider the possibility of a Valsalva movement causing increased IOP when measured with the slit lamp by Goldmann applanation. If so, measurement should be tried via the Tono-Pen or Perkins tonometer or a pneumotonometer with the patient resting back in the examination chair.

Goldmann applanation is considered the criterion standard.[31, 32, 33, 34] However, in cases of increased corneal or scleral rigidity (eg, status post [S/P] keratoplasty, scleral buckle), pneumotonometry or a Tono-Pen measurement can be used and may be more accurate.[35]

IOP varies from hour to hour in any individual. The circadian rhythm of IOP usually causes it to rise in the early hours of the morning; IOP also rises with a supine posture, possibly more so in ocular hypertensive patients.

A difference between eyes of 3 mm Hg or more indicates a greater likelihood of glaucoma. Review previous tonometry readings, if available. Expect an average difference of 10% between individual measurements. Take the measurement in the morning and at night to check the diurnal variation, if possible. (A diurnal variation of more than 5-6 mm Hg may be suggestive of increased risk for POAG.) Early POAG is strongly suspected when a steadily increasing IOP is present.[29]

Studies such as the OHTS have suggested that applanation pressures vary significantly according to corneal thickness and that some patients diagnosed with ocular hypertension actually may be normotensive when correction is made for central corneal thicknesses CCTs.[36, 37, 38] IOP measurements should be interpreted in the context of pachymetry measurements.


Pachymetry is used to measure CCT and is known to influence applanation tonometry values.[31, 39] (See the image below.)

Correction values according to corneal thickness. Correction values according to corneal thickness.

According to the OHTS, pachymetry is now the criterion standard for every baseline examination in patients who are at risk for or are suspected of having glaucoma.[4, 40]

Visual-field/automated perimetry testing

Automated perimetry testing (eg, Humphrey 24-2 visual-field test) should be performed to rule out any glaucomatous visual-field defects. (See the image below.) If there are any visual-field or optic nerve changes consistent with early glaucoma, the patient should no longer be referred to as having ocular hypertension.[41, 42]

Humphrey visual field, right eye, showing patient Humphrey visual field, right eye, showing patient with advanced glaucomatous field loss. Notice both the arcuate extension from the blind spot (Bjerrum scotoma), as well as the loss nasally (nasal step), which often occurs early in the disease process. Courtesy of M. Bruce Shields.

Considerations in visual-field testing

Visual-field defects may not be apparent until more than 40% loss of the nerve fiber layer has occurred. New-onset glaucomatous defects in an individual with previously diagnosed ocular hypertension are found most commonly as an early nasal step, a temporal wedge, or a paracentral scotoma (more frequently superiorly). Generalized depression also can be found. See the image below.

Example of progressive visual field loss over time Example of progressive visual field loss over time (from top to bottom) in a patient with glaucoma. Notice the early appearance of an inferior nasal step and arcuate loss, with progressive enlargement and increasing density of the scotomata over time. Humphrey visual field courtesy of M. Bruce Shields.

Pupillary constriction can reduce retinal sensitivity and mimic field loss.

Software based on the Swedish interactive thresholding algorithm (SITA) may decrease testing time and boost reliability, especially in older patients. Short-wavelength automated perimetry (SWAP) testing, or blue-yellow perimetry, has been proposed as a more sensitive method of detecting visual-field deficits in patients diagnosed with ocular hypertension. Some studies have suggested that SWAP may detect visual loss/progression up to 3-5 years earlier than conventional perimetry, as well as in 12-42% of patients previously diagnosed with only ocular hypertension.[43, 44, 45] Because testing time is lengthened, it may be tiring for some patients; newer SITA-SWAP software was developed to speed up the testing time and thus improve reliability.[46] Some studies have not found SITA-SWAP to be better than standard perimetry testing.[47]

The initial visual field may need to be repeated at least twice on successive visits if initial testing shows low reliability indices. Newer glaucoma progression analysis (GPA) software can help to identify reliable perimetric baselines, and probability-based analyses of subsequent fields can assist in determining if there is true progression over time versus artifact.[48] If the patient is unable to perform automated testing, manual Goldmann perimetry testing may be substituted.



Diagnostic Considerations

Repeat tonometry readings should be taken over time and considered with correlative results of visual field testing, optic nerve examination, and pachymetry measurements before diagnosis or therapy is rendered.

Differential Diagnoses



Imaging Studies

Advances in computerized ocular imaging technology provide useful measures that can assist in glaucoma diagnosis and monitoring.

Imaging technologies such as confocal scanning laser ophthalmoscopy (eg, Heidelberg retina tomogram-HRT), scanning laser polarimetry (GDx), and optical coherence tomography (OCT) provide objective and quantitative measurements of retinal nerve fiber layer (RNFL) that are highly reproducible and show very good agreement with clinical estimates of optic nerve head structure and visual function. As with other technologies, imaging may produce false identification of glaucoma and its progression, thus management decisions should not be based solely on the results of one single test or technology.[49, 50]

In one prospective study of 24 matched eyes, Stratus OCT was found to detect significant differences in RNFL thickness between normal, ocular hypertensive, and glaucomatous eyes.[51]

In a longitudinal study of 857 eyes, the OHTS found HRT imaging to be as effective as stereophotographs for estimating risk of POAG development in ocular hypertensive patients.[52]

Current sensitivities and specificities in these modalities are continuing to improve.

Ultrasonographic Biomicroscopy

Ultrasonographic biomicroscopy (UBM) may prove helpful for obtaining a better view of the angle, iris, and ciliary body structures to rule out anatomic pathology and secondary causes of elevated IOP.[49]

Other Studies

Tonography, used to help determine trabecular outflow facility, is primarily a research tool used in testing pharmacologic agents. Fluorescein angiography, ocular blood flow analysis via laser Doppler flowmetry, color vision measurements, contrast sensitivity testing, and electrophysiologic tests (eg, pattern electroretinograms) currently are used as research tools in the management of ocular hypertension. Routine clinical use is not advocated at this time.[53]



Approach Considerations

A clinical management strategy that targets a 20% reduction in IOP in people with ocular hypertension has been shown to delay or prevent the onset of glaucoma.[54]

Considering the high average monthly cost of glaucoma medication, along with the possible risks of adverse effects or toxic reactions from drugs, inconvenience of use, and sometimes uncertainty of the overall efficacy of prophylactic therapy, there is strong reason not to treat indiscriminately.[55, 56, 57] The OHTS suggests that treatment of patients with IOP higher than 24 mm Hg among those who have a greater than 2% annual risk of developing glaucoma (see the Prognosis section) is cost-effective.[58]

Individualization of therapy is the key; an ideal pressure in one patient may cause glaucomatous damage in another person. Periodically reevaluating the target IOP and performing a review of IOP trends and optic nerve anatomy and function via visual-field testing is necessary to determine whether the patient is consistently maintaining his or her ideal pressure.

Medical care

When risk of progression to POAG is present, treatment with IOP-lowering medications is indicated. See Medication.

Surgical care

Generally, if control cannot be achieved with medications, reconsider the diagnosis of ocular hypertension as that of early POAG. Laser and surgical therapy are not viewed as mainstay treatments for ocular hypertension.


Referral to a subspecialist fellowship trained in glaucoma and/or neuro-ophthalmology should be considered if there is continued inadequate pressure control, loss of visual acuity, visual-field constriction, optic nerve pallor or cupping, associated systemic conditions, or atypical findings.

Follow Up

Depending on the assessed annual risk of developing glaucoma and level of IOP control, patients may need to be seen at intervals ranging from yearly to every 2 months, or even more frequently if there is a marked lack of IOP control.[28]

Long-Term Monitoring

Patients should be observed regularly over their lifetime because some are at increased risk for the development of glaucomatous damage. If treated with medications, the potential for adverse effects or toxic reactions from topical medications exists (see Medication).



Medication Summary

The ideal drug for the treatment of ocular hypertension should effectively lower IOP, produce no adverse effects or systemic exacerbation of disease, be inexpensive, and have once-a-day dosing. Because no medicine currently possesses all of the above, these qualities should be prioritized based on the patient's individual needs and risks, and therapy should then be chosen accordingly.[59]

Older glaucoma medications such as cholinergics (ie, miotics, such as pilocarpine), osmotics, and nonselective adrenergic agonists have a limited role in the treatment of ocular hypertension. They should be considered only if contraindications prevent the use of preferred medications.

In December 2017, the FDA approved netarsudil, a first-in-class inhibitor of rho kinase and norepinephrine transporter, for the treatment of elevated intraocular pressure (IOP) caused by open-angle glaucoma or ocular hypertension. Approval was based on two phase III clinical trials (Rocket 1 and Rocket 2) that enrolled 1,167 patients. Patients were randomized to receive netarsudil once daily (Rocket 1 or Rocket 2) or BID (Rocket 2 only). Timolol was dosed BID in both studies. Treatment with netarsudil once daily produced clinically and statistically significant reductions of IOP from baseline (P< 0.001) and was noninferior to timolol in the per-protocol population with maximum baseline IOP < 25 mm Hg in both studies.[60]

The fixed-dose combination of a Rho-kinase inhibitor and a prostaglandin F2-alpha analogue (netarsudil/latanoprost) was approved by the FDA in 2019. Approval of netarsudil/latanoprost ophthalmic was based on two phase 3 trials, MERCURY 1 (n=718) and MERCURY 2 (n=750). The studies compared the mean IOP after 3 months of once-daily ophthalmic administration of netarsudil/latanoprost, netarsudil, or latanoprost. Patients who received the netarsudil/latanoprost combination achieved an average of 1-3 mm Hg lower mean IOP compared with netarsudil or latanoprost monotherapy. Nearly twice as many patients taking the combination achieved a diurnal IOP of 16 mm Hg or less, and nearly three times as many reached 14 mm Hg or lower compared with latanoprost.[61]

Newer products with neuroprotective effects (eg, memantine, an N -methyl-D-aspartate [NMDA] receptor antagonist) may be available in the future.[62, 63, 64, 65, 66]


Follow-up assessment should be performed 3-4 weeks after beginning therapy.[28] Observe the patient for signs of allergy (eg, hyperemia, rash, follicular reaction). Query patients about the presence of any systemic adverse effects and symptoms. Continue the treatment if effective lowering of IOP has been achieved without adverse effects.[67] Reevaluate the treatment 1-6 months later, depending on the clinical picture.[28]

Modifications in therapy

Some patients do not respond to the chosen therapy, necessitating initiation of another medication with or without discontinuation of the initial medication. When changing therapies, keep in mind that many drugs have a washout period of up to 2-4 weeks (especially beta-blockers), during which time they may still have some IOP-lowering effect or residual systemic response. In addition, some medications (eg, brimonidine) may have an effect that plateaus at 6-8 weeks in some patients.[68, 69]

If the addition of a second agent has been decided, choose one that has a different mechanism of action, so that the 2 drug therapies have an additive effect. Usually, no additive effect is seen if 2 medications from the same drug class are used. When more than 1 topical ophthalmic drug is being used, instruct the patient to administer them at least 10 minutes apart.

Antiglaucoma, Prostaglandin Agonists

Class Summary

These medications work by increasing uveoscleral outflow. Latanoprost, bimatoprost, travoprost, and tafluprost are examples of prostaglandin analogs that may help in IOP reduction.[70, 71, 72] Each of these drugs has its own set of characteristics that may be useful in the clinical setting.

Latanoprost (Xalatan 0.005%)

Latanoprost may decrease IOP by increasing the outflow of aqueous humor. Patients should be informed about possible cosmetic effects to the eye/eyelashes, especially if uniocular therapy is to be initiated.[71]

Bimatoprost ophthalmic solution (Lumigan)

This agent is a prostamide analogue with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Bimatoprost may achieve a large reduction in pressure in many patients, but it is known to cause significant conjunctival hyperemia.

Bimatoprost ophthalmic implant (Durysta)

Intracameral implant indicated to reduce IOP in patients with open-angle glaucoma or ocular hypertension. Provides sustained IOP lowering.

Travoprost ophthalmic solution (Travatan Z)

This agent is a prostaglandin F2-alpha analogue. It is a selective FP prostanoid receptor agonist that is believed to reduce IOP by increasing uveoscleral outflow. Travoprost has been purported to achieve lower IOPs, particularly in African American patients, but these data are the subject of controversy. It may also cause significant conjunctival hyperemia.[72]

Tafluprost (Zioptan)

Tafluprost is a topical, preservative-free, ophthalmic prostaglandin analogue indicated for elevated IOP associated with open-angle glaucoma or ocular hypertension. The exact mechanism by which it reduces IOP is unknown, but it is thought to increase uveoscleral outflow.

Latanoprostene bunod ophthalmic (Vyzulta)

The first prostaglandin analog with one of its metabolites being nitric oxide (NO), is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Latanoprostene bunod is believed to lower intraocular pressure by increasing outflow of aqueous humor through the trabecular meshwork and uveoscleral routes. Intraocular pressure is a major risk factor for glaucoma progression. Reduction of intraocular pressure reduces risk of glaucomatous visual field loss.

Omidenepag isopropyl ophthalmic (Omlonti)

Indicated to reduce elevated intraocular pressure (IOP) in adults with open-angle glaucoma. Selective prostaglandin (EP2) receptor agonist that decreases IOP, possibly by increasing uveoscleral outflow. Additionally, prostaglandin-associated periorbitopathy in patients with glaucoma is not associated with EP2 receptor agonists, but has been a cosmetic problem with prostaglandin F receptor (FP) agonists. Alleviation of periorbitopathy symptoms after switching from an FP agonist to omidenepag isopropyl has been observed. 

Antiglaucoma, Beta-Blockers

Class Summary

These agents decrease aqueous production, possibly by blocking adrenergic beta receptors present in the ciliary body. The nonselective medications in this class can also interact with the beta-receptors in the heart and lungs, causing significant adverse effects.

Betaxolol ophthalmic (Betoptic, Betoptic S)

This agent selectively blocks beta1-adrenergic receptors, with little or no effect on beta2 receptors. It lowers IOP by reducing the production of aqueous humor. The drug may have less effect on the pulmonary system. Its IOP-lowering effect is slightly less than that of nonselective beta-blockers. It may increase optic nerve perfusion and confer neuroprotection.

Carteolol 1%

Carteolol has an intrinsic sympathomimetic activity (partial agonist activity), with possibly less adverse effect on cardiac and lipid profiles.

Timolol 0.25%, 0.5% (Timoptic XE, Istalol)

Timolol may reduce elevated and normal IOP, with or without glaucoma, by reducing the production of aqueous humor. Timolol gel-forming solution (Timoptic XE) usually is administered at night, unless it is used concurrently with latanoprost therapy. Timoptic XE and Istalol (an aqueous solution) are administered daily. Timolol is also available as a combination medication with dorzolamide (Cosopt) and brimonidine (Combigan).

Levobunolol 0.25%, 0.5% (Betagan)

Levobunolol is a nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production and possibly increasing the outflow of aqueous humor.

Metipranolol 0.3% (OptiPranolol)

Metipranolol is a beta-adrenergic blocker that has little or no intrinsic sympathomimetic effect and membrane-stabilizing activity. It also has little local anesthetic activity. The drug reduces IOP by reducing the production of aqueous humor.

Antiglaucoma, Carbonic Anhydrase Inhibitors

Class Summary

By slowing the formation of bicarbonate ions, causing a reduction in sodium and fluid transport, these agents may inhibit carbonic anhydrase in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP. Carbonic anhydrase inhibitors typically have a weaker effect than beta-blockers.

Dorzolamide (Trusopt)

Dorzolamide is a reversible carbonic anhydrase inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably, it slows bicarbonate ion formation, producing a subsequent reduction in sodium and fluid transport.

Systemic absorption can affect carbonic anhydrase in the kidney, reducing hydrogen ion secretion at the renal tubule and increasing renal excretion of sodium, potassium bicarbonate, and water.

Brinzolamide (Azopt)

Brinzolamide catalyzes a reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. It may be used concomitantly with other topical ophthalmic drug products to lower IOP. Brinzolamide is less stinging on instillation secondary to buffered pH.

Acetazolamide (Diamox)

Acetazolamide is primarily used for the treatment of refractory POAG and secondary glaucomas. Because of an increased incidence of adverse effects, it is rarely indicated for ocular hypertension.


Methazolamide reduces aqueous humor formation by inhibiting the enzyme carbonic anhydrase, which results in decreased IOP.

Antiglaucoma, Alpha Agonists

Class Summary

Within this class, the alpha2 selective agonist brimonidine is the most commonly used for the treatment of ocular hypertension.[68] Apraclonidine is another alpha2-selective agonist, but it is believed to have more of an allergic potential, so it rarely is used as a long-term medication. Less selective adrenergics, such as epinephrine and dipivefrin, can have a significantly higher allergic component and other substantial adverse effects, such as exacerbation of hypertension, angina, palpitations, and cystoid macular edema. Because these less selective agents are used infrequently in treating ocular hypertension, they are not discussed here. Alpha2 adrenergic agonists work by decreasing aqueous production.

Brimonidine (Alphagan-P)

Brimonidine is a relatively selective alpha2 adrenergic-receptor agonist that decreases IOP by dual mechanisms, reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine has minimal effect on cardiovascular and pulmonary parameters. A moderate risk of allergic response to this drug exists. Caution should be used in individuals who have developed an allergy to Iopidine. IOP lowering of up to 27% has been reported.

Alphagan-P contains the preservative Purite and has been shown to be much better tolerated than its counterpart, Alphagan.

Apraclonidine 0.5%, 1% (Iopidine)

Apraclonidine is a potent alpha-adrenergic agent that is selective for alpha2 receptors, with minimal cross-reactivity with alpha1 receptors. It suppresses aqueous production and reduces elevated, as well as normal, IOP, whether accompanied by glaucoma or not. Apraclonidine does not have significant local anesthetic activity. It has minimal cardiovascular effects.

Rho Kinase/Norepinephrine Transporter Inhibitor

Class Summary

These agents increase aqueous humor outflow through the trabecular meshwork route.

Netarsudil ophthalmic (Rhopressa)

Indicated for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.

Antiglaucoma, Combos

Class Summary

A combination medication may decrease aqueous humor secretion more than each medication would if used independently as monotherapy and improves patient compliance.[73]

Brimonidine/timolol (Combigan)

This solution contains a selective alpha2 adrenergic-receptor agonist and a nonselective beta adrenergic-receptor inhibitor. Each drug decreases elevated IOP, whether or not it is associated with glaucoma.

Timolol/dorzolamide (Cosopt, Cosopt PF)

Timolol is a nonselective beta-adrenergic receptor blocker that reduces IOP by decreasing aqueous humor secretion. It may also slightly increase outflow facility.

Timolol and dorzolamide administered together twice daily may result in greater IOP reduction than either component would achieve alone. However, the reduction is not as much as it is when the drugs are taken concomitantly, with dorzolamide administered 3 times daily and timolol administered twice daily.

Brinzolamide/brimonidine (Simbrinza)

This combination product contains the carbonic anhydrase inhibitor brinzolamide and the alpha2 adrenergic receptor agonist brimonidine. It is indicated for reduction of elevated intraocular pressure in patients with ocular hypertension.

Latanoprost/netarsudil ophthalmic (Rocklatan)

Fixed-dose combination of a Rho-kinase inhibitor and a prostaglandin F2-alpha analogue. Each drug increases outflow of aqueous humor and thereby lowers IOP. The ophthalmic combination is indicated for reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.


Questions & Answers


What is ocular hypertension (OHT)?

What is the pathophysiology of ocular hypertension (OHT)?

What is the prevalence of ocular hypertension (OHT)?

What are the racial predilections of ocular hypertension (OHT)?

What are the sexual predilections of ocular hypertension (OHT)?

Which age groups are at highest risk for ocular hypertension (OHT)?

What is the prognosis of ocular hypertension (OHT)?

What is the morbidity and mortality associated with ocular hypertension (OHT)?

What is included in patient education about ocular hypertension (OHT)?


What is the focus of the clinical history to evaluate ocular hypertension (OHT)?

What is included a comprehensive eye exam to evaluate ocular hypertension (OHT)?

Which slit-lamp findings are characteristic of ocular hypertension (OHT)?

What is the role of gonioscopy in the evaluation of ocular hypertension (OHT)?

What is the role of a fundus exam in the evaluation of ocular hypertension (OHT)?

What is the role of tonometry in the evaluation of ocular hypertension (OHT)?

What is the role of pachymetry in the evaluation of ocular hypertension (OHT)?

What is the role of automated perimetry testing in the evaluation of ocular hypertension (OHT)?


How is ocular hypertension (OHT) diagnosed?

What are the differential diagnoses for Ocular Hypertension?


What is the role of imaging in the workup of ocular hypertension (OHT)?

What is the role of ultrasonographic biomicroscopy (UBM) in the workup of ocular hypertension (OHT)?

Which research studies are not recommended for the routine workup of ocular hypertension (OHT)?


How is ocular hypertension (OHT) treated?

When are IOP-lower medications indicated in the treatment of ocular hypertension (OHT)?

What is the role of surgery in the treatment of ocular hypertension (OHT)?

Which specialist consultations are beneficial to patients with ocular hypertension (OHT)?

How frequently should patients receive follow-up treatment for ocular hypertension (OHT)?

What is included in the long-term monitoring of ocular hypertension (OHT)?


What is the role of medications in the treatment of ocular hypertension (OHT)?

Which medications in the drug class Antiglaucoma, Combos are used in the treatment of Ocular Hypertension?

Which medications in the drug class Rho Kinase/Norepinephrine Transporter Inhibitor are used in the treatment of Ocular Hypertension?

Which medications in the drug class Antiglaucoma, Alpha Agonists are used in the treatment of Ocular Hypertension?

Which medications in the drug class Antiglaucoma, Carbonic Anhydrase Inhibitors are used in the treatment of Ocular Hypertension?

Which medications in the drug class Antiglaucoma, Beta-Blockers are used in the treatment of Ocular Hypertension?

Which medications in the drug class Antiglaucoma, Prostaglandin Agonists are used in the treatment of Ocular Hypertension?