Ocular hypertension (OHTN) is a clinical condition in which intraocular pressure persistently exceeds 21 mmHg without evidence of optic nerve damage, retinal nerve fiber layer defect, or visual field loss on standard examinations4). According to the glaucoma practice guidelines, it is defined as a condition where intraocular pressure exceeds the statistically determined upper limit of normal but no abnormalities are found in the optic nerve or visual field1). It is the most important modifiable risk factor for progression to primary open-angle glaucoma (POAG) and holds a significant position in ophthalmic practice.
Ocular hypertension is not a homogeneous population; it is considered to include both cases in the prodromal stage of primary open-angle glaucoma and cases where the optic nerve is resistant to intraocular pressure stress. Additionally, many cases have thicker than normal corneas, and some cases have measured intraocular pressure values that are overestimated relative to true intraocular pressure.
Intraocular pressure is approximately normally distributed in the population, with a mean of about 15–16 mmHg (standard deviation about 3.0 mmHg) in adults3). Traditionally, the upper limit of normal intraocular pressure has been defined as the mean plus 2 standard deviations, i.e., 21 mmHg3). However, using only an intraocular pressure threshold is insufficient to distinguish between health and disease, and evaluation of optic nerve structure and function is essential3).
In the Ocular Hypertension Treatment Study (OHTS), patients with ocular hypertension and intraocular pressure (IOP) of 24–32 mmHg were followed long-term. The 5-year conversion rate to primary open-angle glaucoma was 9.5% in the untreated group and 4.4% in the treated group 4). Over approximately 20 years of follow-up, about 45% of participants eventually developed primary open-angle glaucoma, but conversion usually occurred late and was characterized by early mild disease. In the European Glaucoma Prevention Study (EGPS), no significant difference was found between the dorzolamide-treated group (13.4%) and the control group (14.1%), likely due to high dropout rates and small IOP differences between the two groups 1)2).
The 5th edition of the Glaucoma Clinical Practice Guidelines positions ocular hypertension as one of the risk factors for the onset and progression of primary open-angle glaucoma, stating that high baseline IOP and high mean IOP during follow-up are associated with the progression of visual field and optic nerve damage 1). On the other hand, there is insufficient reason to immediately start treatment when IOP is only slightly above the normal upper limit; individualized decisions based on risk factor assessment are required.
The prevalence of ocular hypertension varies by population and differs greatly among reports. It is reported to be about 4.5% in non-Hispanic whites aged 40 and older, and about 3.5% in Latinos 4). The Tajimi Study reported that the prevalence of primary open-angle glaucoma (broad definition) in people aged 40 and older was 3.9% (including 3.6% normal-tension glaucoma), but there are few reports that independently calculate the prevalence of ocular hypertension alone 1). In populations where normal-tension glaucoma is relatively common, the frequency of ocular hypertension tends to be relatively low.
Ocular hypertension is not glaucoma. It is a condition in which only intraocular pressure is elevated, without optic nerve damage or visual field loss 4). However, because it is the greatest modifiable risk factor for primary open-angle glaucoma, regular follow-up is necessary.
Patients with ocular hypertension are asymptomatic. It is often discovered during screening IOP measurements, and is not infrequently detected incidentally during examinations for other conditions, such as health checkups, contact lens prescriptions, or preoperative cataract evaluations. In the chronic course of slowly rising IOP, there are no subjective symptoms such as decreased vision or eye pain, making it difficult for patients to recognize the abnormality. There is no severe eye pain, blurred vision, headache, or nausea as seen in acute primary angle-closure glaucoma, and conjunctival injection or corneal edema is usually absent. This asymptomatic nature is why open-angle glaucoma, including ocular hypertension, is called the “silent disease.”
In the OHTS, optic nerve damage alone (without visual field defects) was observed in 69 eyes, accounting for 55% of endpoints4). Since structural changes often precede detectable visual field loss, detailed evaluation of the optic nerve and RNFL is essential for early detection.
In clinical practice, the following patterns of clinical findings require careful follow-up. Thinning of the optic disc rim, especially notching of the superior and inferior poles, deviation from the ISNT rule, retinal nerve fiber layer defects, enlargement of peripapillary atrophy, and appearance of disc hemorrhages are important early signs suggesting progression from ocular hypertension to primary open-angle glaucoma. OCT quantitative assessments such as peripapillary RNFL thickness, ganglion cell complex thickness, and Bruch’s membrane opening-based rim area (BMO-MRW) are useful for monitoring structural changes over time.
Ocular hypertension is primarily caused by increased resistance to aqueous outflow through the trabecular meshwork. The main site of outflow resistance is localized to the juxtacanalicular connective tissue adjacent to the inner wall of Schlemm’s canal. An imbalance between matrix synthesis and degradation leads to excessive deposition of collagen, fibronectin, and glycosaminoglycans, impeding outflow. Age-related structural changes in trabecular meshwork cells also contribute.
Analyses from OHTS and EGPS have identified the following risk factors1)4).
| Predictor | OHTS | EGPS |
|---|---|---|
| Older age (per 10 years) | HR 1.22 | Significant |
| High intraocular pressure (per 1 mmHg) | HR 1.10 | Significant |
| Large vertical cup-to-disc ratio | HR 1.32 | Significant |
| Thin central corneal thickness (per 40 μm) | HR 1.71 | Significant |
The strongest predictors are thin central corneal thickness (CCT < 555 μm), high intraocular pressure, and large vertical cup-to-disc ratio4). The mean CCT in the OHTS population was approximately 570 μm, and the group with CCT less than 555 μm had a significantly higher risk of developing primary open-angle glaucoma compared to the group with CCT 588 μm or greater4). In cases with central corneal thickness less than 555 μm and intraocular pressure exceeding 25 mmHg, the 5-year risk of conversion to primary open-angle glaucoma has been reported to reach approximately 36%. CCT affects both the estimation of true intraocular pressure and the vulnerability of the optic nerve5).
Corneal hysteresis (CH) is also an important indicator. CH is a viscoelastic property of the cornea measured with devices such as the Ocular Response Analyzer, and multiple studies have shown that it is associated with the risk of glaucoma progression independently of CCT5). Cases with low CH tend to have a higher risk of visual field progression. Note that intraocular pressure correction formulas using CCT values have not been clinically validated, so it is preferable to use CCT as baseline information without calculated correction2).
Characteristics of High-Risk Group
Central corneal thickness < 555 μm: One of the strongest predictors4)
Intraocular pressure > 26 mmHg: Higher baseline IOP increases the conversion rate1)
Large cup-to-disc ratio: Optic disc hemorrhage is also a risk factor for developing primary open-angle glaucoma1)
African descent: Known to have a higher risk of developing primary open-angle glaucoma
Characteristics of Low-Risk Group
Thick CCT: If the cornea is thick, the true intraocular pressure may be lower than the measured value
Small cup-to-disc ratio: Reflects normal optic nerve structure
Young age: However, long-term follow-up is necessary
Prognosis of low-risk group: Very low likelihood of progression even over decades; can be safely observed
The development of ocular hypertension involves family history (relatives with glaucoma), vascular factors, aging, race, refractive error (high myopia), thin corneal thickness, etc. If one eye has already developed glaucoma, the risk of conversion in the fellow eye also increases. Systemic factors such as diabetes, blood pressure fluctuations, sleep apnea syndrome, and migraine are also discussed as glaucoma-related risks, and management of these comorbidities may have significance as secondary prevention. Steroid responsiveness (steroid responder) is also associated with ocular hypertension and subsequent glaucoma development; history and dosage of topical, inhaled, or systemic corticosteroids should always be checked.
Treatment is not always necessary. Management is individualized based on risk stratification1). For low-risk cases, regular follow-up alone may suffice, but for high-risk cases, initiating IOP-lowering treatment can reduce the risk of conversion to primary open-angle glaucoma by approximately 60%4).
The following tests are performed for the diagnosis of ocular hypertension 4).
The sensitivity and specificity of imaging devices for glaucoma diagnosis are around 80%, and final judgment requires comprehensive evaluation by an ophthalmologist. OCT can sometimes detect structural changes before visual field changes, but direct comparison of measurements between different devices is not possible 1)2).
| Differential Diagnosis | Key Points for Differentiation |
|---|---|
| Early Primary Open-Angle Glaucoma | Glaucomatous changes in optic nerve and visual field present |
| Preperimetric glaucoma (PPG) | Structural abnormality on OCT etc. but no visual field defect 1) |
| Normal-tension glaucoma | Glaucomatous changes in optic nerve and visual field with normal intraocular pressure |
| Superior segmental optic nerve hypoplasia (SSOH) | RNFL defect in superior to nasal area, cupping and upward deviation of central retinal vessels |
| Steroid-induced | Check history of steroid use |
| Pigment dispersion syndrome | Pigment deposition in the angle, Krukenberg spindle |
| Pseudoexfoliation syndrome | Pseudoexfoliative material on pupillary margin and anterior lens capsule |
| Secondary to uveitis | Anterior chamber inflammation, keratic precipitates, posterior synechiae |
| Traumatic angle recession | History of trauma and angle recession on gonioscopy |
For the differential diagnosis of secondary ocular hypertension, a detailed history (use of steroid eye drops, inhalation, oral steroids, history of trauma, ocular surgery or intravitreal injection, history of uveitis, systemic diseases) and thorough examination of the anterior segment and angle are essential. In pigment dispersion syndrome, increased transillumination of the iris, uniform pigmentation of the angle, and Krukenberg spindle-shaped pigmentation on the corneal endothelium are observed. In pseudoexfoliation syndrome, white exfoliative material on the pupillary margin and anterior lens capsule is characteristic. Missing these findings can affect treatment strategy and prognosis.
Elevated intraocular pressure alone is insufficient for a diagnosis of primary open-angle glaucoma. The diagnosis of primary open-angle glaucoma requires reproducible structural (optic nerve/RNFL) and/or functional (visual field) glaucomatous damage 4). Ocular hypertension is merely a risk state, and regular follow-up is needed to determine if conversion occurs.
Management of ocular hypertension is generally based on risk assessment and observation, with intraocular pressure-lowering treatment introduced only for cases with risk factors 1). In cases where intraocular pressure is only slightly above the upper limit of normal, there is little strong evidence to initiate treatment. Long-term eye drop therapy involves burdens such as adherence, ocular surface disorders, and medical costs, so the need for treatment is carefully determined based on individual risks and benefits.
Based on the results of OHTS and EGPS, a risk calculator (OHTS/EGPS risk calculator) is available to estimate the 5-year risk of developing primary open-angle glaucoma. Using age, baseline intraocular pressure, CCT, vertical cup-to-disc ratio, and visual field pattern standard deviation, the 5-year risk is calculated to determine treatment initiation and follow-up frequency 1). Generally, early treatment is chosen for high-risk groups (5-year risk >15%), careful observation or individual judgment for moderate-risk groups (5-15%), and observation for low-risk groups (<5%).
In actual risk stratification, decisions are not based solely on a single number; comprehensive consideration is given to the patient’s age and life expectancy, anticipated adherence to intraocular pressure-lowering treatment, side effects of eye drops (ocular surface disorders, conjunctival hyperemia, pigmentation, eyelash elongation, deepening of the eyelid sulcus, allergic reactions), comorbidities, financial burden, and social background. Additionally, findings in each eye should be evaluated independently, and it is not uncommon for only one eye to be considered high risk.
Since structural changes often precede visual field defects, follow-up with OCT RNFL is particularly useful.
When initiating treatment, it is common to set an intraocular pressure (IOP) reduction target of 20–30% from the untreated IOP. The OHTS also aimed for “IOP < 24 mmHg and a reduction of 20% or more,” and in that study, the development of primary open-angle glaucoma in the treatment group was reduced by approximately 60% 4).
First-line medications are selected based on the same principles as for primary open-angle glaucoma. Prostaglandin analogs (PGAs) are the most common first-line choice. Administered once daily at night, they achieve approximately 25–33% IOP reduction, have few systemic side effects, and good compliance. If PGAs are contraindicated or not tolerated, alternatives include alpha-2 agonists (brimonidine), beta-blockers (timolol, levobunolol), carbonic anhydrase inhibitors (dorzolamide, brinzolamide), and Rho kinase inhibitors (netarsudil).
Preservative-free (PF) formulations reduce ocular surface damage and contribute to improved treatment adherence. Since long-term use of benzalkonium chloride (BAK)-containing eye drops can cause corneal and conjunctival epithelial damage, PF formulations are particularly important in conditions requiring long-term management, such as ocular hypertension. The PF tafluprost/timolol fixed combination has achieved both improvement in ocular surface disease and IOP control when stepping down from maximal therapy or stepping up from monotherapy 10). A 36-week extension study of PF latanoprost confirmed long-term safety and tolerability 11). BAK-free latanoprost maintained IOP-lowering efficacy equivalent to BAK-containing latanoprost while reducing conjunctival hyperemia 7).
SLT is a safe and effective treatment option for ocular hypertension. The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial randomized treatment-naïve patients with open-angle glaucoma or ocular hypertension to initial SLT or initial eye drops, showing that SLT as initial therapy provides sustained IOP control and reduces dependence on eye drops over 6 years. In the 6-year LiGHT results, most patients in the initial SLT group remained medication-free at 6 years, with no difference in the frequency of cataract surgery or incisional surgery between groups, demonstrating advantages in reducing adherence burden and cost-effectiveness.
SLT uses a Q-switched Nd:YAG laser at 532 nm wavelength, selectively targeting pigmented cells in the trabecular meshwork. It lowers IOP by improving aqueous outflow through macrophage migration and extracellular matrix remodeling while minimizing thermal damage. Side effects are limited to transient anterior chamber inflammation and IOP elevation, and retreatment is possible if the effect diminishes. Unlike the older argon laser trabeculoplasty (ALT), which causes scarring of the trabecular meshwork through thermal coagulation, SLT has better repeatability.
Secondary ocular hypertension refers to a condition in which only intraocular pressure (IOP) elevation occurs without glaucomatous optic neuropathy, caused by factors such as corticosteroid use, exfoliation material, pigment dispersion, uveitis, trauma, post-intraocular surgery, pre-neovascular glaucoma stage, and elevated episcleral venous pressure. Treatment and elimination of the underlying cause is the first priority; if the cause cannot be removed, drug therapy, laser treatment, or surgery similar to that for primary open-angle glaucoma is selected. When using steroid eye drops, oral steroids, or intravitreal steroid injections, regular IOP monitoring before and during administration is essential.
Aqueous humor is produced by the non-pigmented ciliary epithelium, flows from the posterior chamber through the pupil into the anterior chamber, and exits the eye through the angle. IOP is determined by the balance between aqueous humor production, outflow, and episcleral venous pressure. Most cases of ocular hypertension are due to reduced aqueous outflow; increased production is rarely the main cause.
Aqueous humor is drained mainly via the trabecular outflow pathway (conventional pathway) and the uveoscleral outflow pathway. In the trabecular pathway, aqueous humor passes through the trabecular meshwork into Schlemm’s canal, then through collector channels and the episcleral venous plexus to return to the systemic circulation. Ocular hypertension results from increased resistance in this outflow pathway. The contribution of the uveoscleral pathway decreases with age, so in older individuals, dependence on the trabecular pathway tends to increase.
The greatest outflow resistance is localized in the juxtacanalicular connective tissue (JCT) and the inner wall endothelium of Schlemm’s canal. When the balance between matrix synthesis and degradation shifts toward progressive matrix accumulation, this region thickens. Excessive deposition of collagen, fibronectin, and glycosaminoglycans impedes aqueous outflow. Aging, oxidative stress, and enhanced TGF-β2 signaling are suggested to be involved.
Trabecular meshwork endothelial cells may stiffen and adopt a more contractile morphology due to increased actin stress fibers. When cells contract, channels narrow, reducing the capacity to accommodate aqueous outflow. Activation of the Rho-ROCK signaling pathway has been shown to contribute to trabecular cell stiffening and contraction, and Rho kinase inhibitors have been developed as therapeutic agents that intervene in this pathway. These age-related structural and cellular changes lead to chronic IOP elevation in eyes with open angles.
Central corneal thickness (CCT) and corneal hysteresis (CH) affect both the difference between Goldmann applanation tonometry readings and true intraocular pressure, as well as optic nerve vulnerability 5). Thicker corneas tend to yield higher readings than the true value, while thinner corneas yield lower readings. Additionally, low CH acts as an independent risk factor for glaucoma progression even after CCT correction. This is thought to be due to similar biomechanical properties of connective tissue in the cornea and lamina cribrosa.
Xiao & Qiu (2025) retrospectively reviewed 171 cases of ocular hypertension (OHT) after intravitreal dexamethasone implant (Ozurdex) 8). OHT occurred most frequently 2–3 months after injection, with an incidence of 23.3%. It was managed with eye drops (10.0%), SLT (1.2%), and MIGS (4.1%); no cases required trabeculectomy or tube shunt surgery 8). Risk increased in patients aged 60 years or older (OR 6.65), and was lower in retinal vein occlusion cases compared to DME cases (OR 0.07) 8).
Canestraro et al. (2021) reported two cases of elevated intraocular pressure due to presumed trabeculitis during immune checkpoint inhibitor (ICI) therapy 9). Despite mild anterior chamber inflammation, IOP rose to 52 mmHg and 33 mmHg. Discontinuation of ICI, topical steroids, and antiglaucoma medications achieved resolution of inflammation and normalization of IOP within 7–10 days 9). In one case, no recurrence of trabeculitis was observed after re-administration of ICI (at a lower dose) 9).
Prathapan et al. (2023) prospectively studied 46 eyes after vitrectomy with silicone oil injection 6). The incidence of OHT at 90 days postoperatively was 21.7%. Age <50 years (OR 147.1), pseudophakia (OR 12.3), and surgical time ≤40 minutes (OR 23.8) were independent risk factors for early OHT; pre-existing glaucoma (OR 7.3) was the only independent risk factor for late OHT 6).
Gaur et al. (2022) reported a case of a 43-year-old male who developed bilateral acute iris depigmentation (BADI) and ocular hypertension (IOP 48/44 mmHg) after COVID-19 infection 12). With antiglaucoma medications and steroid eye drops, IOP normalized after 10 days, and visual acuity recovered to 20/20 after 2 months 12). BADI is a rare disease associated with viral infections and certain antibiotics, and is one of the differential diagnoses of OHT that ophthalmologists should recognize 12).
From the integrated analysis of OHTS and EGPS, a 5-year prediction model for onset was developed using age, IOP, CCT, vertical cup-to-disc ratio, and visual field pattern standard deviation, and is widely used as an aid to clinical decision-making 5). In recent years, efforts to improve prediction accuracy using machine learning models that combine OCT-derived structural indices, fundus images, and genetic information are progressing, and application to personalized follow-up and treatment initiation decisions is expected. AI-based fundus photograph analysis is beginning to show promising results for early detection and progression prediction of glaucomatous optic nerve changes.
Lowering IOP is the only established treatment, but a certain number of cases progress despite IOP reduction. Neuroprotective interventions such as vitamin B3 (nicotinamide), citicoline, Rho kinase inhibitors, sildenafil citrate, and neurotrophic factors are being investigated in basic and clinical research. Currently, there is no established evidence for neuroprotective treatment in ocular hypertension, and IOP management remains the central treatment.
Yes. Steroid-induced ocular hypertension is a known side effect, caused by increased aqueous outflow resistance due to biochemical and structural changes in the trabecular meshwork. Ocular hypertension has also been reported in 23.3% of cases after dexamethasone implant 8). Regular IOP monitoring is important during steroid use.
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