eMedicine Specialties > Ophthalmology > Intraocular Pressure

Ocular Hypertension

Jerald A Bell, MD, Staff Physician, Department of Ophthalmology, Billings Clinic; Glaucoma Director, Leadership Council Member, Physician Advocate for Personal Service Excellence Committee
Judie F Charlton, MD, Director - Division of Glaucoma, Professor, Department of Ophthalmology, West Virginia University

Updated: Nov 10, 2008

Introduction

Background

The term ocular hypertension (OHT) often has been used as a generic term, referring to any situation in which intraocular pressure (IOP) is greater than 21 mm Hg. Such usage could refer to a variety of conditions in which it occurs (eg, traumatic hyphema, orbital edema, postoperative viscoelastic retention, intraocular inflammation, corticosteroid use, pupillary block, idiopathic causes). 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. Consequently, clarification of the term is the first topic of mention.

The definition of this condition has evolved throughout the latter part of the 20th century. It was used as early as 1962 by Drance, but it was not defined in English language publications until 1966 by Perkins and others, with definitions similar to the following:

Ocular hypertension is a condition in which the below criteria are present:

• An intraocular pressure greater than 21 mm Hg in one or both eyes as measured by applanation tonometry on 2 or more occasions
• No glaucomatous defects on visual field testing
• Normal appearance of the optic disc and nerve fiber layer
• Open angles on gonioscopy, with no history of angle closure
• Absence of any ocular disease contributing to the elevation of pressure

Beginning in the 1970s, controversy began to erupt on the usefulness of the term. Despite the clear-cut early definitions, ocular hypertension had come to mean different things to different people. Ophthalmologists became concerned with the ambiguity of the term. People, such as Hitchings, began to stress the point of not reading too much into the term, as its definition "does not imply an ocular hypertensive will not develop glaucoma, nor does this label imply that an early stage of glaucoma exists. Such a patient with this label may remain without other signs of glaucoma, or may become normotensive, or may develop glaucomatous cupping with or without field loss, and become a case of frank glaucoma."

Consequently, since the late 1970s, several (including George Spaeth) have advocated total disuse of the term, secondary to this inherent ambiguity or what has been called an elegant hedge. They feel such a term implies that the physician has future knowledge of the patient's course, when, in fact, the opposite is true. Hence, they prefer the term glaucoma suspect, which is believed to more adequately convey the uncertainty regarding the diagnosis and prognosis. On the other hand, many feel any use of a phrase with the word glaucoma in it implies a malignant meaning, or a certainty that the patient is at a very high risk for developing glaucoma. A classic discussion of what should be appropriate terminology (including even the choice early open-angle glaucoma without damage) can be seen in the multiple editorials by Chandler and Grant, Kolker and Becker, Shaffer, and Phelps in Archives of Ophthalmology dating back to 1977.

In this article, discussion is limited to ocular hypertension as referring to a prolonged state of the eye(s) meeting the above 5 criteria, without other signs of primary open-angle glaucoma (POAG), and from no known specific causation. Ocular hypertension should not be considered as a disease entity by itself, but rather a term describing a subset of individuals who should be observed more closely than the general population for the onset of glaucomatous damage.

See related CME at Treated Open-Angle Glaucoma and Ocular Hypertension Associated With Risk of Cardiovascular-Related Death.

Pathophysiology

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. The exact role that IOP plays in combination with these other factors and their significance as to the initiation and progression of subsequent glaucomatous neuronal damage and cell death over time is still under debate; the precise mechanism is still a hot topic of discussion.

Nevertheless, IOP is the only factor that has been able to be successfully manipulated clinically, so categorizing and managing patients based on their IOP has forced the issue of ocular hypertension and when it should be treated to prevent optic nerve damage.

Several studies over the years have shown that, as IOP rises above 21 mm Hg, the percentage of patients developing visual field loss increases rapidly, most notably at pressures higher than 26-30 mm Hg. A patient with an IOP of 28 mm Hg is about 15 times more likely to develop field loss than an ocular hypertensive with a pressure of 22 mm Hg. Thus, a population described as ocular hypertensive should not be thought of as a homogeneous population.

Before classifying a patient strictly as ocular hypertensive, the following factors should be considered when categorizing where a patient's measurements fall:

• The variability of tonometry measurements per examiner (usually found to be about 10%, or 1-2 mm Hg)
• The effect corneal thickness has on accuracy of IOP measurements (see Other Tests) 
• The diurnal variation of IOP (often highest in the early morning hours, but maximum IOP can be at any time of day in some patients)
• In addition, remember that normal eyes have a diurnal variation of approximately 3-4 mm Hg, while glaucomatous eyes have an even higher variation (>10 mm Hg). Note that multiple readings should be taken over time and should be considered with correlative evidence of visual field and optic nerve examination before any diagnosis or therapy is rendered.

Other points of importance when considering a diagnosis of ocular hypertension include the following:

• Disc cupping and nerve fiber layer losses of up to 40% have been shown to occur before actual visual field loss has been detected. Therefore, visual field examination cannot be the sole tool used to determine when a patient is no longer ocular hypertensive but, instead, has frank glaucoma, and it should not be used in isolation as the benchmark for treatment.
• Some evidence suggests ocular hypertensives have a higher variability of IOP with postural changes than in patients with ocular hypertension.
• Basic and clinical science research continues to look into factors that contribute to the development and prognosis of the ocular hypertensive patient.

Frequency

United States

Multiple population studies (including the Framingham, Beaver Dam, Baltimore, Rotterdam, Barbados, and Egna-Neumarkt studies) have been performed to estimate the prevalence of eye disease, including POAG and ocular hypertension.

Estimates of the prevalence of glaucoma in studies involving only the United States suggest the following: glaucoma is a leading cause of irreversible blindness, second only to macular degeneration; only one half of the people who have glaucoma may be aware that they have the disease; and more than 2.25 million Americans aged 40 years and older have POAG. These studies estimate that 3-6 million people in the United States alone, including 4-10% of the population older than 40 years, will have IOPs of 21 mm Hg or higher, without detectable signs of glaucomatous damage using current clinical testing.

Prospective studies over the last 20 years have helped to characterize the ocular hypertensive population. Roughly 0.5-1% per year of those patients with elevated IOP will develop glaucoma over a period of 5-10 years. However, the risk may be even less than 1% per year, now that ophthalmoscopic and perimetric techniques for detecting glaucomatous damage have improved significantly. Ocular hypertension has a 10-15 times greater prevalence than POAG (as defined by visual field loss). Out of every 100 patients older than 40 years, about 10 will have pressures higher than 21 mm Hg, and 1 of those patients will have glaucoma. See Medical therapy versus observation in Medical Care and Media files 10-11.

International

Glaucoma is the second leading cause of blindness in the world (surpassed only by cataracts, a reversible condition). More than 3 million people are bilaterally blind from POAG worldwide, and more than 2 million people will develop POAG each year.

Mortality/Morbidity

• Over a 5-year period, several studies have shown the incidence of glaucomatous damage in ocular hypertensives to be about 2.6-3% for IOPs 21-25 mm Hg, 12-26% for IOPs 26-30 mm Hg, and approximately 42% for those higher than 30 mm Hg. The OHTS has further clarified this data. Patients with ocular hypertension have an overall risk of 10% over 5 years of developing glaucoma. This risk can be cut in half by medical treatment. Pachymetry results further stratify this risk into specific subsets.
• In year 2000, an estimated 2.47 million people in the United States had frank glaucoma and more than 130,000 were legally blind because of this disease. These statistics alone emphasize the need to identify and monitor closely those at risk of glaucomatous damage, especially ocular hypertensives.
• One specific morbidity associated with ocular hypertension is that of retinal vascular occlusions, which may occur in approximately 3% of ocular hypertensives. It has been suggested that ocular hypertensives older than 65 years be treated to keep their pressures below 25 mm Hg.

Race

• Black individuals are considered to have a 3-4 times higher prevalence of POAG, and they are believed to be more susceptible to optic nerve damage. There is also a higher prevalence of larger cup-to-disc ratios in the normal black population as compared with white control subjects.
• The data are more conflicting when it comes to ocular hypertension specifically. Over 4 years, the Barbados Eye Study showed a 5 times higher incidence of developing glaucoma in a group of ocular hypertensives as compared with a predominantly white population.
• Some population studies have found mean IOP in blacks to be higher than in Caucasian control subjects. Others, such as the Baltimore Eye Study, found no difference. Consequently, further study needs to be completed to clarify this issue.

Sex

Differing reports exist on sexual predilection. Although some age-controlled studies have reported significantly higher mean IOP values in women than in men, others have failed to find such a difference. Some also suggest that although women could be at higher risk for ocular hypertension (especially after menopause), men with ocular hypertension may be at a higher risk for glaucomatous damage.

Age

• 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.
• Elevated pressure in a young person is a cause for concern because an individual would have longer exposure time to high pressures over a lifetime, with more likelihood of developing optic nerve damage.

Clinical

History

• 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
• Past medical history - Any surgeries or pertinent vasculopathic systemic illnesses
• Current medications, including any hypertensive medications (which may indirectly cause fluctuation of IOP) or topical/systemic corticosteroids
• Risk factors for glaucomatous optic neuropathy  
  • Strongly implicated risk factors
    • History of elevated IOP, advanced age (particularly persons >50 y), African American descent, positive family history of glaucoma (first-degree relative; especially correlative if present in a sibling [relative risk 3.7-fold higher than if no family history of glaucoma]), and myopia
    • Be specific when asking family history - Which family members? Did actual visual loss from glaucoma occur? Did other causes of visual field loss occur? Are they under control on one or more medications? Did they require surgery for adequate control?
  • Possibly implicated risk factors - Systemic cardiovascular disease, diabetes mellitus, migraine headache, systemic hypertension, and vasospasm
• Anecdotal risk factors - Obesity, smoking, alcohol, and history of stress or anxiety (no definitive link to ocular hypertension)

Physical

Screening should be performed at least every 3-5 years in asymptomatic patients aged 40 years or younger and more often if the person is African American or older than 40 years. For those with multiple risk factors, evaluation/monitoring should be performed on a more frequent basis, as appropriate.

A standard comprehensive eye examination, such as that outlined in the American Academy of Ophthalmology (AAO) Preferred Practice Patterns, should be performed on the initial visit. If there are any visual field or optic nerve changes consistent with early glaucoma, then the patient should be diagnosed as having such and should no longer be referred to as ocular hypertensive.

Emphasis during the examination should be on the following points to rule out early POAG or secondary causes of glaucoma:

• Visual acuity: Compare visual acuity with previous known acuities (if declining, rule out frank POAG or secondary causes of vision loss, whether from cataracts, age-related macular degeneration [ARMD], ocular surface disorders [eg, dry eye], or adverse effects from topical medications [especially if using miotics]).
• Pupils: The presence/absence of afferent pupillary defect (Marcus-Gunn) should be seen.
• Slit lamp examination of the anterior segment
  • Cornea: Look for signs of microcystic edema (found only with a sudden elevation of IOP); keratic precipitates; pigment on endothelium (Krukenberg spindle); and congenital anomalies.
  • Anterior chamber: Examine for cell or flare, uveitis, hyphema, and angle closure.
  • Iris: Transillumination defects, iris atrophy, synechiae, rubeosis, ectropion uveae, iris bombé, difference in iris coloration bilaterally (eg, Fuchs heterochromic iridocyclitis), or pseudoexfoliation (PXF) material may be observed.
  • Lens: Examine for cataract progression (ie, phacomorphic glaucoma, PXF, phacolytic glaucoma with a Morgagnian cataract).
  • Optic nerve/nerve fiber layer: Stereoscopically examine for evidence of glaucomatous damage, including cup-to-disc ratio in horizontal and vertical meridians (describe by color and slope, and diagram, if needed); appearance of disc; progressive enlargement of the cup; evidence of nerve fiber layer damage with red-free filter; notching or thinning of disc rim, particularly at the superior and inferior poles (because nerve fibers at the superior and inferior poles of the disc can often be affected first); pallor; presence of hemorrhage (most common inferotemporally); asymmetry between discs; parapapillary atrophy (possible association with development of glaucoma); or congenital nerve abnormalities.
  • Fundus: Other abnormalities that could account for any nonglaucomatous visual field defects or vision loss present (eg, disc drusen, optic pits, retinal disease), vitreous hemorrhage, or proliferative retinopathy.
• Baseline stereo fundus photographs: Obtain baseline stereo fundus photographs for future reference/comparison; if unavailable, record representative drawings.
• Tonometry (see also Tonometric methods in Other Tests) 
  • IOP varies from hour to hour in any individual. The circadian rhythm of IOP usually causes it to rise most in the early hours of the morning; IOP also rises with a supine posture, possibly more so in ocular hypertensives.
  • When checking IOP, record all of the following: measurements for both eyes, the method used (Goldmann applanation is the criterion standard), and the time of the measurement.
  • Review previous tonometry readings, if available (eg, Is the reading reproducible? What method was used to obtain the reading? What was the time of day? Where does it fall on the diurnal pressure curve? Do both the eyes have similar measurements?).
  • In patients who are obese, consider the possibility of a Valsalva movement causing an increased IOP when measured with the slit lamp by Goldmann applanation. Measurement should be tried via Tono-Pen, Perkins, or pneumotonometer with the patient resting back in the examination chair.
  • A difference between the 2 eyes of 3 mm Hg or more indicates a greater likelihood of glaucoma. Expect an average of 10% difference between individual measurements. Repeat the measurements on at least 2-3 occasions before deciding on a treatment plan. 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.
  • Pachymetry affects applanation tonometry values and, therefore, should be checked on the initial examination.
• Gonioscopy: Gonioscopy should be performed to rule out angle-closure or secondary causes of IOP elevation, such as angle recession, pigmentary glaucoma, and PXF.
• Pachymetry: Pachymetry is used to measure central corneal thickness (CCT). According to the OHTS, pachymetry is now the criterion standard for every baseline examination in patients who are at risk for or suspected of having glaucoma (see Media file 11).
• Visual field testing
  • Perform automated threshold testing (eg, Humphrey 24-2) to rule out any glaucomatous visual field defects. If the patient is unable to perform automated testing, Goldmann testing may be substituted.
  • If the patient is unable to perform automated testing, Goldmann testing may be substituted.
• Remember the following caveats regarding visual field analysis (see Other Tests):
  • New-onset glaucomatous defects in an individual with previously diagnosed ocular hypertension are found most commonly as an early nasal step, temporal wedge, or a paracentral scotoma (more frequent superiorly); generalized depression related to IOP level also can be found.
  • Swedish interactive thresholding algorithm (SITA)-based software algorithms may decrease testing time and boost reliability, especially in older patients.
  • SWAP (short wavelength automated perimetry or blue-yellow perimetry) may provide a more sensitive method of detecting visual field deficits in those diagnosed as ocular hypertensive. If the Humphrey visual field testing results are normal, SWAP should be considered to help detect visual field loss earlier. Studies suggest 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. Because the testing time may be lengthened, it may be tiring for some patients. However, new SITA-SWAP algorithm software may speed up the testing time and thus improve reliability.
  • Examination results must take into account that visual field defects may not be apparent until more than 40% loss of the nerve fiber layer has occurred. Therefore, base the therapy on the overall clinical picture and not on visual field testing alone (see Treatment). 
  • Document the pupil size at each testing session, as constriction can reduce retinal sensitivity and mimic progressive field loss.
  • The risk factors, specifically for the development of glaucomatous field loss in ocular hypertension, have been studied, and it was found that several presumed risk factors (ie, presence of hypertension, diabetes, refractive error, race, family history of glaucoma, gender, smoking or ethanol use, disc area) were not found to be of significance for prediction of eventual field loss.
  • Significant positive predictive factors of field loss included higher IOP, older age, presence of a disc crescent, larger cup-to-disc ratio, smaller rim-disc area ratio, and cup asymmetry. Consequently, the relationship of risk factors for ocular hypertension compared with that of actual field loss development is much more complex than has been previously presumed.
  • The initial visual field baseline may need to be repeated at least twice on successive visits, especially if initial testing shows low reliability indices. Newer glaucoma progression analysis (GPA) software can help identify reliable perimetric baselines, and probability-based analyses of subsequent fields can assist in determining if there is true progression over time versus artifact. In follow-up, if there is a low risk of onset of glaucomatous damage, then repeat testing may be performed once a year. If there is a high risk of impending glaucomatous damage, then testing may be adjusted to as frequent as every 2 months.

Causes

See Pathophysiology.

Differential Diagnoses

Workup

Imaging Studies

• Fluorescein angiography, ocular blood flow analysis via laser Doppler flowmetry, color vision measurements, contrast sensitivity testing, and electrophysiological 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.
• Ultrasound biomicroscopy (UBM) may prove to be helpful in the future for obtaining a better view of the angle, iris, and ciliary body structures to rule out anatomical pathology and secondary causes of elevated IOP.
  

Other Tests

• Tonometric methods
  • Goldmann applanation tonometry is considered the criterion standard. 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.
  • Studies, such as the OHTS, suggest that applanation pressures may vary significantly depending on the corneal thickness and that some patients diagnosed with ocular hypertension actually may be normotensive when corrected for corneal thickness. Pachymetry may play a role in determining a fudge factor by which to adjust each patient's IOP measurement.
  • Frequency doubling perimetry (also termed frequency doubling technology or FDT, which is enhanced with MATRIX software), scanning laser polarimetry (GDx), scanning retinal tomography (HRT), and ocular coherence tomography (OCT) are all relatively new technologies that may be able to detect nerve fiber layer loss at an earlier stage in the glaucomatous disease process, thus screening out more people who currently are misdiagnosed as having ocular hypertension instead of early POAG. Current sensitivities and specificities are continuing to improve, but more baseline data are needed to determine in what setting these new techniques will prove to be most useful.
• Other tests of historical and research interest include the following:
  • Tonography, which has been used to help determine trabecular outflow facility, is primarily a research tool used in testing pharmacologic agents.
  • Provocative testing, such as the water-drinking test, was used to try to differentiate those patients who would develop early open-angle glaucoma. It was found to be of no aid in distinguishing those patients who would develop visual field defects from those who would not.

Treatment

Medical Care

Some physicians incorrectly treat all elevated IOPs higher than 21 mm Hg with topical medication. Other physicians do not treat unless there is evidence of optic nerve damage. Although, as mentioned before, nerve fiber layer loss of up to 40% may occur before visual field defects occur, so do not treat based on visual field testing alone. Most physicians select and treat those patients believed to be at greatest risk for developing glaucoma (most common approach). See History and Physical (visual field testing) for a list of risk factors for glaucomatous field loss.

In any case, the goal of treatment is reduction of the pressure before it causes glaucomatous loss of vision. Some advocate a policy of close observation without treatment simply because most patients are at low risk of visual loss from ocular hypertension. One collaborative glaucoma study showed that only 1.7% of eyes developed visual field loss over a 1- to 13-year period. 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, incidence of noncompliance, and uncertainty of the overall efficacy of prophylactic therapy, there is a strong reason not to treat indiscriminately.

• Several questions should be asked when considering treatment: Is the elevated pressure significant? Will this patient develop visual loss if left untreated? Is the treatment worth the risk of adverse effects of the medications?
  • One should consider treatment more strongly if the patient reliability or the consequences of missing field loss is an issue (eg, poor reliability on visual field examination, one-eyed patient, poor availability for follow-up care, younger patient, patient whose optic nerve is difficult to visualize, history of vascular occlusion).
  • Treatment is highly recommended if signs of damage consistent with glaucomatous optic neuropathy (eg, disc hemorrhage; visible nerve fiber layer defects; notching or vertical ovalization of the cup; asymmetric cupping, especially if >0.7) are observed. Progressive cupping, even in the absence of visual field loss, can be glaucoma and should be treated as such. Otherwise, it depends on the assessment of risk factors and benefit of therapy to the patient, as to whether therapy should be initiated.
  • Discuss the pros and cons of treatment versus observation with the patient. Individualization of therapy is the key; an ideal pressure in one patient may cause glaucomatous damage in another patient. All the risk factors and systemic conditions, life expectancy of the patient, quality of life issues, and the patient's desire for therapy should be weighed when considering treatment.
  • Because of the high risk of optic nerve damage, most ophthalmologists treat if pressures are consistently higher than 28-30 mm Hg. If treatment is based on a high IOP only, then it should be ensured that the risks of treatment do not exceed the risk of the disease.
  • Other reasons to treat include such symptoms as halos, blurred vision, or pain, or recent elevation of IOP, with continuing elevation on successive visits.
  • The initiation of a monocular trial (see Medication) also may be useful in helping to decide whether to treat (ie, if the medication is effective in achieving good pressure reduction without adverse effects, that might argue in favor of treatment, instead of just observation).
  • Considering all of the above, there is still no consensus on what is the appropriate medical treatment for preventing or delaying the damage due to POAG when a patient has only elevated IOP and no other signs of POAG. No one has yet been able to define conclusively which subgroups are the ones that will develop damage if left untreated, as opposed to those who will not sustain damage even if not treated.
• Medical therapy versus observation
  • The question of medical therapy versus observation is being addressed by the OHTS, which is a multicenter, prospective, randomized, controlled, clinical trial studying more than 1600 research subjects to evaluate the safety and efficacy of medical treatment in preventing or delaying onset of visual field loss and/or optic nerve damage in patients with ocular hypertension who are at moderate risk for developing POAG.
  • The OHTS medical therapy goal for the treated group is stepped therapy to reduce IOP by at least 20% from the average baseline IOP with its treated absolute value being 24 mm Hg or lower.
  • So far, the results show a 10% risk over 5 years of developing glaucoma in patients with baseline IOP of 24-31 mm Hg. This risk was reduced to 5% with medical therapy.
  • The OHTS also revealed the importance of pachymetry as a diagnostic tool and in the workup (see Media files 10-11). 
  • Several sources agree on this initial goal of 20-25% reduction, while some specialists believe that more absolute numbers of lower than 15 should be the goal of treatment. The IOP goal must be set independently for each patient, depending on the risk factors, because an IOP level for one person with minimal risk factors may be far too high for a patient with multiple risks for sustaining glaucomatous damage.
  • Other regimens have been suggested. For minimal risk factors, consider lowering IOP by 20-30%; if a moderate number of risk factors are present, lower by 30-40%; and, in cases of numerous risk factors with markedly elevated pressures, reduction in the 40-60% range may need to be achieved to prevent neuronal loss.
  • If the patient is older than 65 years, consider treatment to keep IOP 25 mm Hg or lower, secondary to 3% risk of vascular occlusion in ocular hypertensives.
  • In any case, periodically reevaluate the target IOP, and perform regular review of IOP trends to determine whether the patient is consistently maintaining that goal.
• The following is one suggested time guideline for therapy and follow-up testing based on initial IOP level (adjust frequency of follow-up testing as needed based on the number of risk factors and clinical picture):
  • IOP 28 mm Hg or higher: Treat patients with therapy (see Medication) and have them return in 1 month to assess if the treatment is effective and that there are no adverse effects. If the goal is reached, then perform follow-up testing every 3-4 months.
  • IOP 26-27 mm Hg: Complete follow-up testing in 2-3 weeks for rechecking pressure. If IOP is still within 3 mm of the initial reading, then continue follow-up testing every 3-4 months with visual field and dilated optic nerve evaluation at least once a year. If IOP is lower, then consider a longer time between the pressure checks, making sure to recheck IOP at different times of the day on subsequent appointments.
  • IOP 22-25 mm Hg: Perform follow-up testing 2-3 months later for recheck of IOP at different times of the day (ie, 8 am, 11 am, 1 pm, and 4 pm). If it is still within 3 mm of the initial reading at second visit, then perform follow-up testing at 6 months with Humphrey visual field testing and dilated optic nerve evaluation; repeat testing at least yearly.
• Other caveats concerning follow-up testing include the following:
  • If a visual field defect becomes apparent on testing, confirm with repeat (possibly multiple) examinations during future office visits before using it as a basis for the treatment of presumed early POAG.
  • Perform gonioscopy at least once every 1-2 years if a significant increase in IOP occurs or if miotic therapy is instituted.
  • Repeat optic disc photos after the initial examination if a change in disc appearance is noted (or every 1-2 years if available).
    • Technologic and financial barriers, as well as increasing lack of trained ophthalmic staff, are making optic disc photos more difficult to obtain in many practices.
    • Whether nerve fiber layer imaging technologies (instead of recurring, serial optic disc photos) are sufficient for mainstream nontertiary ophthalmology practices is still under debate.
  • Retinal tomography, ocular coherence tomography, and/or laser polarimetry should be measured at baseline and then every 1-2 years. The results should be correlated with visual field results, IOP measurements, and examination findings.

Surgical Care

• Generally, if control cannot be achieved with 1-2 medications, reconsider the diagnosis of ocular hypertension as possibly that of early POAG.
• Laser and surgical therapy are not viewed to be the mainstay treatment for ocular hypertension because risks of both laser trabeculoplasty and surgery are higher than the actual risk of developing glaucomatous damage from ocular hypertension.
• Selective laser trabeculoplasty
  • Selective laser trabeculoplasty (SLT) uses a Q-switched 532 Nd:YAG laser to selectively target pigmented cells of the trabecular meshwork in a nonthermal manner, increasing fluid outflow and thereby lowering IOP.
  • The 3-nanosecond high-energy specific wavelength of light used induces the same cell replacement mechanism as traditional argon laser therapy (ALT) but without the destructive burning and obliteration of structural support tissue in the meshwork. The short pulse of the laser does not allow time for heat to spread to other cells. SLT delivers just enough energy to the trabecular meshwork to target specific melanin-rich cells, without incurring collateral thermal damage and scarring to adjacent nonpigmented trabecular meshwork cells and underlying trabecular beams. When treated with SLT, a primarily biologic response is induced in the trabecular meshwork that involves the release of cytokines that trigger macrophage recruitment as well as other changes leading to IOP reduction.
  • The laser beam bypasses surrounding tissue leaving it undamaged by light. Unlike ALT, SLT can be repeated several times. Whereas patients treated with ALT can receive only 2 treatments in their lifetime, patients treated with SLT can receive 2 treatments a year.
  • SLT requires a specially designed laser, as follows:
    • A short pulse to allow for thermal relaxation
    • Precise wavelength for optimal melanin absorption
    • Sufficient energy to heat melanin to the point that it releases cytokines
    • Sufficient spot size to ensure full coverage at the trabecular meshwork

Consultations

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

Medication

The ideal drug for treatment of ocular hypertension should have the following characteristics: (1) effectively lower IOP, (2) no adverse effects or systemic exacerbation of disease, and (3) inexpensive with once-a-day dosing. However, because no medicine possesses all of the above, these qualities must be prioritized based on the patient's individual needs and risks; then, therapy should be chosen accordingly.

Older glaucoma medications, such as cholinergics (ie, miotics, such as pilocarpine) and osmotics, as well as nonselective adrenergic agonists, have a limited role in the treatment of ocular hypertension and should only be considered if adverse effects prevent the use of the above-described medications.

Newer products having possible neuroprotective effects (eg, memantine, which is an N-methyl-D-aspartate [NMDA] receptor antagonist), as well as new multiple-agent combinations, are likely to be available in the future. Their role in the treatment of ocular hypertension will have to be studied as they become available for use.

Once a medication has been initiated, perform close follow-up care to assess its effect. Perform initial follow-up care 3-4 weeks after the beginning of therapy. Recheck IOP at the drug's peak and trough times to see if target IOP has been reached and is maintained throughout the day. Observe for signs of allergy to the medication (eg, hyperemia, skin rash, follicular reaction). Query patients about the presence of any systemic adverse effects and symptoms. Continue the treatment if a therapeutic trial has shown effective lowering of IOP without adverse effects. Reevaluate 2-4 months later, depending on the clinical picture.

Consider a monocular therapeutic trial when first initiating the medical therapy, since IOP in the other eye can be used as a baseline control to gauge effect of a medication (particularly useful in patients with a widely fluctuating diurnal curve). A difference of more than 4 mm Hg between the 2 eyes after treatment is strongly suggestive of a clinical effect. However, some agents (especially beta-blockers) may have crossover effects on the other eye even with monocular treatment, and so clinical correlation must be kept in mind. If monocular therapy is found to be effective, consider initiating binocular therapy.

Some medications (eg, latanoprost, brimonidine) may have an effect that plateaus at 6-8 weeks in certain patients; keep this in mind when scheduling further follow-up examinations. Other patients will be nonresponders to some therapies. If this occurs, discontinue the medication and initiate a new drug. While discontinuing or changing therapies, keep in mind that many drugs have a wash-out period of up to 2-4 weeks (especially beta-blockers), during which they may still have some IOP-lowering effect or residual systemic response.

If one medication is not adequate in reaching the target pressure, choose a second medication that has a different mechanism of action, so that the 2 drug therapies will have an additive effect. (Usually, no additive effect is seen if 2 medications from the same drug class are used.)

Administer a specific plan of pharmacotherapy only after the possible effects of the systemic medications (eg, beta-blockers, calcium channel blockers, ACE inhibitors) that a patient is taking have been taken into consideration.

See AAO's Ophthalmology monograph #13 for an in-depth description of particular drugs.

Carbonic anhydrase inhibitors (CAIs)

By slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport, it may inhibit carbonic anhydrase (CA) in the ciliary processes of the eye. This effect decreases aqueous humor secretion, reducing IOP. These agents typically have a weaker effect than beta-blockers. The more commonly used drug of this type for the treatment of ocular hypertension is in the combination medication Cosopt (which may be tried if single agent beta-blocker therapy has had suboptimal results).

Dorzolamide (Trusopt)

Reversible carbonic anhydrase inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably, it slows bicarbonate ion formation with subsequent reduction in sodium and fluid transport.
Systemic absorption can affect carbonic anhydrase in the kidney, reducing hydrogen ion secretion at renal tubule, and increasing renal excretion of sodium, potassium bicarbonate, and water.
Less stinging on instillation, secondary to buffered pH.

Dosing

Adult

1 gtt in affected eye(s) bid/tid; usually tid if using as a single agent, bid if used in conjunction with other agents

Pediatric

Not established

Interactions

Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CAIs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with long-term administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy); oral dosage form can cause paresthesias, malaise, anorexia, and poor tolerance of carbonated beverages; there is rare incidence of aplastic anemia associated with its use (baseline CBC and at least 1 follow-up CBC should be considered in the first 6 mo of treatment to monitor therapy)

Brinzolamide (Azopt)

Catalyzes reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. May use concomitantly with other topical ophthalmic drug products to lower IOP. If more than 1 topical ophthalmic drug is being used, administer drugs at least 10 min apart.

Dosing

Adult

1 gtt in affected eye(s) tid

Pediatric

Not established

Interactions

May have additive systemic effects if patient is already on oral CAIs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with long-term administration (discontinue therapy and evaluate patient before restarting therapy)

Acetazolamide (Diamox, Diamox Sequels)

Primarily used only for the treatment of refractory POAG and secondary glaucomas. Because of increased incidence of adverse effects, rarely indicated for treatment of ocular hypertension.

Dosing

Adult

Tablets: 125-250 mg PO qid
Sequels: 500 mg PO bid

Pediatric

Not established; suggested dose is as in adults

Interactions

Can decrease therapeutic levels of lithium and alter excretion of drugs (amphetamines, quinidine, phenobarbital, salicylates) by alkalinizing urine

Contraindications

Documented hypersensitivity; hepatic disease; severe renal disease; adrenocortical insufficiency; severe pulmonary obstruction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients with impaired hepatic function may go into coma; may cause substantial increase in blood glucose in some diabetic patients

Timolol/dorzolamide (Cosopt)

Carbonic anhydrase inhibitor that may decrease aqueous humor secretion, causing a decrease in IOP. Presumably slows bicarbonate ion formation with subsequent reduction in sodium and fluid transport.
Timolol is a nonselective beta-adrenergic receptor blocker that decreases IOP by decreasing aqueous humor secretion and may slightly increase outflow facility.
Both agents administered together bid may result in additional IOP reduction compared with either component administered alone, but reduction is not as much as when dorzolamide tid and timolol bid are administered concomitantly.

Dosing

Adult

1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CAIs

Contraindications

Documented hypersensitivity; COPD; CHF; asthma; cardiac conduction defects; breastfeeding

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with chronic administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy); product may have sulfites, which may cause allergic-type reactions in susceptible patients

Methazolamide (Neptazane)

Reduces aqueous humor formation by inhibiting enzyme carbonic anhydrase, which results in decreased IOP.

Dosing

Adult

25-50 mg PO bid/tid initially; not to exceed 150 mg PO bid

Pediatric

Not established

Interactions

May increase toxicity of salicylate, digoxin; coadministration with other diuretics may induce hypokalemia; decreases effects of lithium and alter excretion of other drugs by alkalinizing urine

Contraindications

Documented hypersensitivity; renal impairment

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in respiratory acidosis and diabetes mellitus; impairs mental alertness and/or physical coordination; hematuria, glycosuria, polyuria, hepatic insufficiency, bone marrow suppression, thrombocytopenia/purpura, agranulocytosis, urticaria, pruritus, and rash may occur

Adrenergic agonists

Of this class, the alpha2-selective agonist, brimonidine, is the most commonly used for the treatment of ocular hypertension. Apraclonidine is an alpha2-selective agonist but 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, also can have a significantly higher allergic component and other substantial adverse effects, such as exacerbation of hypertension, angina, palpitations, or cystoid macular edema (CME). Because these less selective agents are used infrequently in treating ocular hypertension, they are not discussed herein. Alpha2-adrenergic agonists work by decreasing aqueous production.

Brimonidine (Alphagan, Alphagan-P)

Relatively selective alpha2-adrenergic receptor agonist, decreases IOP by dual mechanisms. Reduces aqueous humor production and increases uveoscleral outflow. 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% reported.
The brand Alphagan-P contains the preservative Purite and has been shown to be much better tolerated than its counterpart Alphagan.

Dosing

Adult

1 gtt in affected eye(s) bid/tid; a bid frequency is used initially, especially if in combination with other classes of agents; in single-agent therapy, tid dosing is used most often when bid frequency does not adequately control IOP

Pediatric

Not established

Interactions

Coadministration with topical beta-blockers may further decrease IOP; tricyclic antidepressants may decrease effects of brimonidine; CNS depressants, such as barbiturates, opiates, and sedatives, may potentiate effects of brimonidine

Contraindications

Documented hypersensitivity; patients receiving MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate or precipitate ocular irritation, topical sensitivity, vasovagal attack, and optic nerve ischemia in patients with advanced glaucomatous optic neuropathy; caution if patient is aphakic, pseudophakic, or has history of CME or allergic response to Iopidine; systemic adverse effects include dry mouth, fatigue, drowsiness, allergic (follicular) conjunctivitis, contact dermatitis

Apraclonidine 0.5%, 1% (Iopidine)

Potent alpha-adrenergic agent selective for alpha2-receptors with minimal cross-reactivity to alpha1-receptors. Suppresses aqueous production. Reduces elevated, as well as normal, intraocular pressure (IOP) whether accompanied by glaucoma or not. Apraclonidine is relatively selective alpha-adrenergic agonist that does not have significant local anesthetic activity. Has minimal cardiovascular effects.

Dosing

Adult

1 gtt of 0.5% or 1% in affected eye(s) tid

Pediatric

Not established

Interactions

Monitor pulse and BP frequently when giving cardiovascular drugs; not for use concurrently with MAO inhibitors

Contraindications

Documented hypersensitivity; patients on MAO inhibitors or have taken them in the past 14 d

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate or precipitate ocular irritation, topical sensitivity, vasovagal attack and optic nerve ischemia in patients with advanced glaucomatous optic neuropathy

Prostaglandin analogs

Newer class of medication that works by increasing uveoscleral outflow.

Unoprostone (Rescula), bimatoprost (Lumigan), and travoprost (Travatan) are examples of newly approved drug analogues similar to prostaglandins that may help in IOP reduction. All 3 of these drugs are new alternatives in the armamentarium of medications to treat elevated IOP. Limited data are available on these drugs, but each has its own set of characteristics that may be useful in the clinical setting. Unoprostone has been shown to decrease pressure approximately 10-15% and may work partially through traditional outflow channels. Bimatoprost may achieve a large reduction in pressure in many patients but has been known to cause significant conjunctival hyperemia. Travoprost has been purported to achieve lower IOPs, particularly in patients of African American descent, but these data are in doubt and the subject of controversy. It also may cause significant conjunctival hyperemia.

Latanoprost (Xalatan 0.005%)

May decrease IOP by increasing outflow of aqueous humor. Patients should be informed on possible cosmetic effects to eye/eyelashes, especially if uniocular therapy is to be initiated.

Dosing

Adult

1 gtt in affected eye(s) qhs

Pediatric

Not established

Interactions

Coadministration with eye drops containing the preservative thimerosal may reduce effects (administer at intervals of 5 min between applications); effect may be additive if used with miotic agents (eg, pilocarpine), which decrease uveoscleral outflow

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Patients who are pregnant or breastfeeding should use caution because knowledge of effects on pediatric patients is limited; caution in history of uveitis or CME and monocular therapy because lash and iris color changes may occur; increased pigmentation of iris and eyelashes; increased growth (hypertrichosis) of eyelashes and adjacent hair; conjunctival hyperemia; may promote baseline intraocular inflammation

Bimatoprost ophthalmic solution (Lumigan)

A prostamide analogue with ocular hypotensive activity. Mimics the IOP-lowering activity of prostamides via the prostamide pathway. Used to reduce IOP in open-angle glaucoma or ocular hypertension.

Dosing

Adult

1 gtt of 0.03% solution in affected eye(s) hs; not to exceed 1 dose/d

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; may increase eyelash growth; may cause bacterial keratitis; caution in uveitis or macular edema; do not instill if wearing contact lenses

Travoprost ophthalmic solution (Travatan)

Prostaglandin F2-alpha analog. Selective FP prostanoid receptor agonist believed to reduce IOP by increasing uveoscleral outflow. Used to treat open-angle glaucoma or ocular hypertension.

Dosing

Adult

1 gtt in affected eye(s) hs; not to exceed 1 dose/d

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; pregnancy

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Commonly causes ocular hyperemia; may cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; may increase eyelash growth; may cause bacterial keratitis; caution in uveitis or macular edema; do not instill if wearing contact lenses

Unoprostone ophthalmic solution (Rescula)

Prostaglandin F2-alpha analog. Selective FP prostanoid receptor agonist believed to reduce IOP by increasing uveoscleral outflow. Used to treat open-angle glaucoma or ocular hypertension.

Dosing

Adult

1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Commonly causes ocular hyperemia; may cause permanent increase in pigment to iris (ie, increases brown pigment) and eyelid; may increase eyelash growth; may cause bacterial keratitis; caution in uveitis or macular edema; do not instill if wearing contact lenses

Beta-adrenergic blockers

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

Betaxolol 0.25% (Betoptic-S)

Levobetaxolol (Betaxon) -- Selectively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors. Reduces IOP by reducing production of aqueous humor. May have less pulmonary effects. IOP-lowering effect is slightly less than nonselective beta-blockers. May increase optic nerve perfusion and confer neuroprotection.

Dosing

Adult

1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

May have additive systemic effects if patient is already on systemic beta-blockers

Contraindications

Documented hypersensitivity; bronchial asthma; severe COPD; sinus bradycardia; second- and third-degree AV block; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients; may exacerbate or precipitate heart block, asthma, COPD, and mental changes (especially in elderly patients); may cause blurred vision and eye ache; should be avoided in women who are breastfeeding because beta-blockers can be found concentrated in breast milk

Carteolol 1% (Ocupress)

Has an intrinsic sympathomimetic activity (partial agonist activity), with possibly less cardiac and lipid profile adverse effects.

Dosing

Adult

1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; bronchial asthma; sinus bradycardia; second- and third-degree AV block; severe COPD; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients; may exacerbate or precipitate heart block, asthma, COPD, and mental changes especially in elderly patients); may cause blurred vision and eye ache; should be avoided in women who are breastfeeding because beta-blockers can be found concentrated in breast milk

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

May reduce elevated and normal IOP, with or without glaucoma by reducing production of aqueous humor. Timolol gel-forming solution (Timoptic XE) usually is administered at night, unless used concurrently with latanoprost therapy.
The brands Timoptic XE and Istalol are both administered qd. However, Timoptic XE is a gel-forming solution, while Istalol is an aqueous solution.

Dosing

Adult

Timolol: 1 gtt in affected eye(s) bid
Timolol XE: 1 gtt in affected eye(s) qd

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; bronchial asthma; sinus bradycardia; second- and third-degree AV block; severe COPD; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients; may exacerbate or precipitate heart block, asthma, COPD, and mental changes (especially in elderly patients); may cause blurred vision and eye ache; should be avoided in women who are breastfeeding because beta-blockers can be found concentrated in breast milk

Levobunolol 0.25%, 0.5% (Betagan, AKBeta)

Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production and possibly increasing outflow of aqueous humor.

Dosing

Adult

1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; bronchial asthma; severe COPD; sinus bradycardia; second- and third-degree AV block; overt cardiac failure; cardiogenic shock

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients; may exacerbate or precipitate heart block, asthma, COPD, and mental changes (especially in elderly patients); may cause blurred vision and eye ache; should be avoided in women who are breastfeeding because beta-blockers can be found concentrated in breast milk

Metipranolol 0.3% (OptiPranolol)

Beta-adrenergic blocker that has little or no intrinsic sympathomimetic effects and membrane-stabilizing activity. Has little local anesthetic activity. Reduces IOP by reducing production of aqueous humor.

Dosing

Adult

1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects)

Contraindications

Documented hypersensitivity; sinus tachycardia; cardiac failure; cardiogenic shock; second- and third-degree AV block

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Product may have sulfites, which may cause allergic-type reactions in susceptible patients; may exacerbate or precipitate heart block, asthma, COPD, and mental changes (especially in elderly patients); may cause blurred vision and eye ache; should be avoided in women who are breastfeeding because beta-blockers can be found concentrated in breast milk

Less-selective sympathomimetics

These less-selective adrenergic drugs increase outflow of aqueous humor through the trabecular meshwork and possibly through the uveoscleral outflow pathway, probably by a beta2-agonist action. Up to one third of patients will not respond to these drugs.

Less-selective adrenergics, such as epinephrine, dipivefrin, and memantine also can have a significantly higher allergic component and other substantial adverse effects, such as exacerbation of hypertension, angina, palpitations, or cystoid macular edema (CME). These less-selective agents are used infrequently. Memantine, increases outflow of aqueous humor through the trabecular meshwork and possibly through the uveoscleral outflow pathway, probably by a beta2-agonist action.

Epinephrine 0.5%, 1%, 2% (Epifrin)

Lowers IOP by increasing outflow and reducing production of aqueous humor. Used as adjunct to miotic or beta-blocker therapy. Combination of miotic and sympathomimetic will have additive effects in lowering IOP.

Dosing

Adult

1 gtt in affected eye(s) qd/bid

Pediatric

Not established

Interactions

Increases toxicity of beta- and alpha-blocking agents

Contraindications

Documented hypersensitivity; narrow- or shallow-angle glaucoma; aphakia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiac arrhythmias

Dipivefrin (AKPro, Propine)

Prodrug converted to epinephrine in eye by enzymatic hydrolysis. Appears to act by decreasing aqueous production and enhancing outflow facility. Has same therapeutic effect as epinephrine with fewer local and systemic adverse effects. May be used as an initial therapy or as an adjunct with other antiglaucoma agents for the control of IOP.

Dosing

Adult

1 gtt in affected eye(s) bid

Pediatric

Not established

Interactions

Increased or synergistic effects are seen when used concurrently with agents that lower intraocular pressure

Contraindications

Documented hypersensitivity; narrow-angles; dilation of pupil may predispose patient to attack of angle-closure glaucoma

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Macular edema occurs in up to 30% of aphakic patients treated with epinephrine; discontinuation of treatment generally results in reversal of maculopathy; caution in vascular hypertension

Memantine (Namenda, Axura)

Indicated for moderate-to-severe Alzheimer disease; currently still in Phase 3 trial for possible neuroprotective systemic treatment of glaucoma, although as of now, this is a non-FDA approved off-label use of the drug. N-methyl-D-aspartate (NMDA) antagonist. NMDA receptor stimulation in the CNS by glutamate (an excitatory amino acid) is hypothesized to contribute to Alzheimer symptoms, as well as apoptosis (programmed cell death) and neuronal degeneration.

Dosing

Adult

5 mg PO qd initially; gradually titrate to a target dose of 20 mg/d using the following dosage regimen (allow at least 1-2 wk between each dosage increase, particularly if side effects, such as headache or nausea, occur): 5 mg PO bid; then, 5 mg PO qam and 10 mg PO qpm; then, 10 mg PO bid

Pediatric

Not indicated

Interactions

Coadministration with drugs causing alkaline urine (eg, sodium bicarbonate, carbonic anhydrase inhibitors) may decrease clearance by 80%, thus accumulation and toxicity may occur (eg, caution should be used in patients also on acetazolamide [Diamox] or other carbonic anhydrase inhibitors, although memantine has been used clinically with acetazolamide without morbidity when patients are monitored appropriately and dosages adjusted); coadministration with other NMDA antagonists (eg, amantadine, ketamine, dextromethorphan) may increase toxicity risk; concurrent use with other drugs renally eliminated via tubular secretion (eg, hydrochlorothiazide, triamterene, cimetidine, ranitidine, quinidine, nicotine) may alter plasma levels of either drug

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Common adverse effects include dizziness (7%), headache (6%), and constipation (5%); predominantly excreted renally, no data support use with severe renal impairment

Beta-blocker / Alpha Agonist Combination

Combination solution may further decrease aqueous humor secretion compared to each solution used as monotherapy, while improving compliance.

Brimonidine/timolol (Combigan)

Selective alpha-2 adrenergic receptor agonist with a nonselective beta-adrenergic receptor inhibitor. Each of them decrease elevated IOP, whether or not associated with glaucoma.

Dosing

Adult

1 gtt in affected eye(s) bid approximately q12h

Pediatric

Not established

Interactions

May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects); coadministration with topical beta-blockers may further decrease IOP; tricyclic antidepressants may decrease effects of brimonidine; CNS depressants (eg, barbiturates, opiates, sedatives) may potentiate effects of brimonidine

Contraindications

Documented hypersensitivity; bronchial asthma; sinus bradycardia; second- and third-degree AV block; severe chronic obstructive pulmonary disease; overt cardiac failure; cardiogenic shock; patients receiving MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-blockade may potentiate muscle weakness that is consistent with certain myasthenic symptoms (eg, diplopia, ptosis, generalized weakness); product may have sulfites, which may cause allergic-type reactions in certain susceptible persons; caution in cardiovascular disease, depression, cerebral or coronary insufficiency, orthostatic hypotension, and Raynaud syndrome; punctal occlusion may help minimize adverse effects; caution if patient is aphakic, pseudophakic, or has history of CME or allergic response to Iopidine

Follow-up

Further Outpatient Care

• Depending on the amount of optic nerve damage and level of IOP control, patients with ocular hypertension may need to be seen from every 2 months to yearly, even sooner if a marked lack of IOP control is present. Follow-up studies/examinations should be performed as detailed under Treatment. 
• Glaucoma still should be a concern in people with elevated IOP in the presence of normal discs and visual fields or in people who have normal IOP with suspicious-looking discs and fields. These patients should be observed closely because they are at an increased risk for development of glaucomatous damage. SWAP visual field testing may also play a role, because it may help detect visual field defects earlier in these otherwise healthy patients.

Complications

• With poor control of IOP, continuing changes to the optic nerve and visual field occur.

Prognosis

• Prognosis is very good for patients with ocular hypertension. With careful follow-up care and compliance with therapy, most patients with ocular hypertension do not progress to POAG, and they retain good vision throughout their lifetime.

Patient Education

• Patient education is essential for successful treatment of glaucoma. The patient who understands the chronic, potentially progressive nature of glaucoma is more likely to comply with therapy. 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 excellent patient education resources, visit eMedicine's Glaucoma Center. Also, see eMedicine's patient education articles Ocular Hypertension and Normal-Tension Glaucoma.

Miscellaneous

Medicolegal Pitfalls

• Failure to diagnose glaucoma is a possible cause of litigation. Adherence to the American Academy of Ophthalmology's Preferred Practice Patterns is recommended and encouraged.
  • Tonometry alone is insufficient for screening; physicians also must examine optic nerve appearance in correlation with visual field results and pachymetry.
  • Suspected changes in the appearance of the optic nerves should be monitored closely via serial disc photos and serial computerized nerve fiber layer analysis, as well as through careful observation on follow-up visits, with further testing as required.
• Good communication, patient education, and appropriately documented informed consent before any procedure are the best prophylaxis against litigation from suboptimal outcomes.

Multimedia

Media file 1: Diagram of intraocular pressure distribution, with a visible skew to the right (somewhat exaggerated compared to the actual distribution). Note that, while uncommon, there can be field loss among individuals with pressures in the upper teens. Also, note how the average pressure among those with glaucoma is in the low 20s, even though most individuals with pressures in the low 20s do not have glaucoma. Used by permission from Survey of Ophthalmology.

Media file 2: Flowchart for evaluation of a patient with suspected glaucoma. Used by permission of the American Academy of Ophthalmology.

Media file 3: 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

Media file 4: 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.

Media file 5: 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.

Media file 6: 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.

Media file 7: 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.

Media file 8: 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.

Media file 9: Advanced glaucomatous damage with increased cupping and substantial pallor of the optic nerve head. Courtesy of M. Bruce Shields.

Media file 10: Correction values according to corneal thickness.

Media file 11: Ocular hypertension study (OHTS). Percentage of patients who developed glaucoma during this study, stratified by baseline intraocular pressure (IOP) and central corneal thickness (CCT).

References

1. Allen RC, Netland PA, eds. American Academy of Ophthalmology. In: Glaucoma Medical Therapy: Principles and Management. 1999.

2. Alward WL. The genetics of open-angle glaucoma: the story of GLC1A and myocilin. Eye. Jun 2000;14 (Pt 3B):429-36. [Medline].

3. American Academy of Ophthalmology. Preferred practice patterns: primary open angle glaucoma suspect and POAG. 1995-1996.

4. Ang GS, Bochmann F, Townend J, et al. Corneal biomechanical properties in primary open angle glaucoma and normal tension glaucoma. J Glaucoma. Jun-Jul 2008;17(4):259-62. [Medline].

5. Annette H, Kristina L, Bernd S, et al. Effect of central corneal thickness and corneal hysteresis on tonometry as measured by dynamic contour tonometry, ocular response analyzer, and Goldmann tonometry in glaucomatous eyes. J Glaucoma. Aug 2008;17(5):361-5. [Medline].

6. Ashaye AO, Adeoye AO. Characteristics of patients who dropout from a glaucoma clinic. J Glaucoma. Apr-May 2008;17(3):227-32. [Medline].

7. Aung T, Chew PT, Yip CC, et al. A randomized double-masked crossover study comparing latanoprost 0.005% with unoprostone 0.12% in patients with primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. May 2001;131(5):636-42. [Medline].

8. Azuara-Blanco A, Burr JM. Assessment of glaucoma imaging technology. Ophthalmology. Jul 2008;115(7):1266-7; author reply 1267-8. [Medline].

9. Bakri SJ, McCannel CA, Edwards AO, et al. Persisent ocular hypertension following intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol. Jul 2008;246(7):955-8. [Medline].

10. Bathija R, Gupta N, Zangwill L, et al. Changing definition of glaucoma. J Glaucoma. Jun 1998;7(3):165-9. [Medline].

11. Beckers HJ, Schouten JS, Webers CA, et al. Side effects of commonly used glaucoma medications: comparison of tolerability, chance of discontinuation, and patient satisfaction. Graefes Arch Clin Exp Ophthalmol. Oct 2008;246(10):1485-90. [Medline].

12. Bengtsson B. A new rapid threshold algorithm for short-wavelength automated perimetry. Invest Ophthalmol Vis Sci. Mar 2003;44(3):1388-94. [Medline].

13. Bengtsson B, Heijl A. Normal intersubject threshold variability and normal limits of the SITA SWAP and full threshold SWAP perimetric programs. Invest Ophthalmol Vis Sci. Nov 2003;44(11):5029-34. [Medline].

14. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. May 2008;115(5):763-8. [Medline].

15. Berisha F, Feke GT, Hirose T, et al. Retinal blood flow and nerve fiber layer measurements in early-stage open-angle glaucoma. Am J Ophthalmol. Sep 2008;146(3):466-472. [Medline].

16. Bramley T, Peeples P, Walt JG, et al. Impact of vision loss on costs and outcomes in medicare beneficiaries with glaucoma. Arch Ophthalmol. Jun 2008;126(6):849-56. [Medline].

17. Brandt JD. Corneal thickness in glaucoma screening, diagnosis, and management. Curr Opin Ophthalmol. Apr 2004;15(2):85-9. [Medline].

18. Brandt JD, Beiser JA, Gordon MO, et al. Central corneal thickness and measured IOP response to topical ocular hypotensive medication in the Ocular Hypertension Treatment Study. Am J Ophthalmol. Nov 2004;138(5):717-22. [Medline].

19. Brandt JD, Beiser JA, Kass MA, et al. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. Oct 2001;108(10):1779-88. [Medline].

20. Brubaker RF. Mechanism of action of bimatoprost (Lumigan). Surv Ophthalmol. May 2001;45 Suppl 4:S347-51. [Medline].

21. Bruhn RL, Stamer WD, Herrygers LA, et al. Relationship between Glaucoma and Selenium Levels in Plasma and Aqueous Humor. Br J Ophthalmol. Jun 12 2008;[Medline].

22. Brusini P, Salvetat ML, Zeppieri M, et al. Comparison of ICare tonometer with Goldmann applanation tonometer in glaucoma patients. J Glaucoma. Jun 2006;15(3):213-7. [Medline].

23. Cantor L. American Academy of Ophthalmology. In: Section 10: Glaucoma. In: Basic and Clinical Science Course. 1996.

24. Chandler PA, Grant WM. 'Ocular hypertension' vs open-angle glaucoma. Arch Ophthalmol. Apr 1977;95(4):585-6. [Medline].

25. Chauhan BC. Endothelin and its potential role in glaucoma. Can J Ophthalmol. Jun 2008;43(3):356-60. [Medline].

26. Chen TC, Ahn Yuen SJ, Sangalang MA, et al. Retrobulbar chlorpromazine injections for the management of blind and seeing painful eyes. J Glaucoma. Jun 2002;11(3):209-13. [Medline].

27. Cheung W, Guo L, Cordeiro MF. Neuroprotection in glaucoma: drug-based approaches. Optom Vis Sci. Jun 2008;85(6):406-16. [Medline].

28. Chihara E. Assessment of true intraocular pressure: the gap between theory and practical data. Surv Ophthalmol. May-Jun 2008;53(3):203-18. [Medline].

29. Chihara E. Assessment of true intraocular pressure: the gap between theory and practical data. Surv Ophthalmol. May-Jun 2008;53(3):203-18. [Medline].

30. Cioffi GA, Latina MA, Schwartz GF. Argon versus selective laser trabeculoplasty. J Glaucoma. Apr 2004;13(2):174-7. [Medline].

31. Colton T, Ederer F. The distribution of intraocular pressures in the general population. Surv Ophthalmol. Nov-Dec 1980;25(3):123-9. [Medline].

32. Cox JA, Mollan SP, Bankart J, et al. Efficacy of antiglaucoma fixed combination therapy versus unfixed components in reducing intraocular pressure: a systematic review. Br J Ophthalmol. Jun 2008;92(6):729-34. [Medline].

33. Craven ER, Walters TR, Williams R, et al. Brimonidine and timolol fixed-combination therapy versus monotherapy: a 3-month randomized trial in patients with glaucoma or ocular hypertension. J Ocul Pharmacol Ther. Aug 2005;21(4):337-48. [Medline].

34. Deokule S, Weinreb RN. Relationships among systemic blood pressure, intraocular pressure, and open-angle glaucoma. Can J Ophthalmol. Jun 2008;43(3):302-7. [Medline].

35. Dhaliwal JS, Mason BF, Kaufman SC. Long-term use of topical tacrolimus (FK506) in high-risk penetrating keratoplasty. Cornea. May 2008;27(4):488-93. [Medline].

36. Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv Ophthalmol. Mar-Apr 2000;44(5):367-408. [Medline].

37. ElMallah MK, Asrani SG. New ways to measure intraocular pressure. Curr Opin Ophthalmol. Mar 2008;19(2):122-6. [Medline].

38. ElMallah MK, Asrani SG. New ways to measure intraocular pressure. Curr Opin Ophthalmol. Mar 2008;19(2):122-6. [Medline].

39. Eskridge JB. Ocular hypertension or early undetected glaucoma?. J Am Optom Assoc. Sep 1987;58(9):747-69. [Medline].

40. Filippopoulos T, Rhee DJ. Novel surgical procedures in glaucoma: advances in penetrating glaucoma surgery. Curr Opin Ophthalmol. Mar 2008;19(2):149-54. [Medline].

41. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol. Jan 2007;143(1):9-22. [Medline].

42. George MK, Emerson JW, Cheema SA, et al. Evaluation of a modified protocol for selective laser trabeculoplasty. J Glaucoma. Apr-May 2008;17(3):197-202. [Medline].

43. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. Jun 2002;120(6):714-20; discussion 829-30. [Medline].

44. Gordon MO, Kass MA. The Ocular Hypertension Treatment Study: design and baseline description of the participants. Arch Ophthalmol. May 1999;117(5):573-83. [Medline].

45. Greenfield DS, Girkin C, Kwon YH. Memantine and progressive glaucoma. J Glaucoma. Feb 2005;14(1):84-6. [Medline].

46. Greenfield DS, Weinreb RN. Role of optic nerve imaging in glaucoma clinical practice and clinical trials. Am J Ophthalmol. Apr 2008;145(4):598-603. [Medline].

47. Grus F, Sun D. Immunological mechanisms in glaucoma. Semin Immunopathol. Apr 2008;30(2):121-6. [Medline].

48. Grus FH, Joachim SC, Wuenschig D, et al. Autoimmunity and glaucoma. J Glaucoma. Jan-Feb 2008;17(1):79-84. [Medline].

49. Halkiadakis I, Kipioti A, Emfietzoglou I, et al. Comparison of optical coherence tomography and scanning laser polarimetry in glaucoma, ocular hypertension, and suspected glaucoma. Ophthalmic Surg Lasers Imaging. Mar-Apr 2008;39(2):125-32. [Medline].

50. Hernandez R, Rabindranath K, Fraser C, et al. Screening for open angle glaucoma: systematic review of cost-effectiveness studies. J Glaucoma. Apr-May 2008;17(3):159-68. [Medline].

51. Hodapp EA, Anderson DR. Treatment of early glaucoma. In: Focal Points. 1986;4(4).

52. Holz HA, Lim MC. Glaucoma lasers: a review of the newer techniques. Curr Opin Ophthalmol. Apr 2005;16(2):89-93. [Medline].

53. Hoskins HD Jr. The management of elevated intraocular pressure with normal optic discs and visual fields. II. An approach to early therapy. Surv Ophthalmol. May-Jun 1977;21(6):479, 489-93. [Medline].

54. Inatani M, Iwao K, Inoue T, et al. Long-term relationship between intraocular pressure and visual field loss in primary open-angle glaucoma. J Glaucoma. Jun-Jul 2008;17(4):275-9. [Medline].

55. Jacobi S, Dubielzig RR. Feline primary open angle glaucoma. Vet Ophthalmol. May-Jun 2008;11(3):162-5. [Medline].

56. Jamil AL, Mills RP. Glaucoma tube or trabeculectomy? That is the question. Am J Ophthalmol. Jan 2007;143(1):141-2. [Medline].

57. Johnson TD, Zimmerman TJ. Ocular hypertension, glaucoma suspect, preglaucoma, or glaucoma? Synopsis of views. Ann Ophthalmol. Nov 1986;18(11):313-4. [Medline].

58. Juzych MS, Chopra V, Banitt MR, et al. Comparison of long-term outcomes of selective laser trabeculoplasty versus argon laser trabeculoplasty in open-angle glaucoma. Ophthalmology. Oct 2004;111(10):1853-9. [Medline].

59. Kahook MY, Noecker RJ. Comparison of corneal and conjunctival changes after dosing of travoprost preserved with sofZia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears. Cornea. Apr 2008;27(3):339-43. [Medline].

60. Kass MA. When to treat ocular hypertension. Surv Ophthalmol. Dec 1983;28 Suppl:229-34. [Medline].

61. Kass MA, Hart WM Jr, Gordon M, et al. Risk factors favoring the development of glaucomatous visual field loss in ocular hypertension. Surv Ophthalmol. Nov-Dec 1980;25(3):155-62. [Medline].

62. Kaufmann C, Bachmann LM, Thiel MA. Comparison of dynamic contour tonometry with goldmann applanation tonometry. Invest Ophthalmol Vis Sci. Sep 2004;45(9):3118-21. [Medline].

63. Kiekens S, Veva De Groot, Coeckelbergh T, et al. Continuous positive airway pressure therapy is associated with an increase in intraocular pressure in obstructive sleep apnea. Invest Ophthalmol Vis Sci. Mar 2008;49(3):934-40. [Medline].

64. Krupin T, Liebmann JM, Greenfield DS, et al. The Low-pressure Glaucoma Treatment Study (LoGTS) study design and baseline characteristics of enrolled patients. Ophthalmology. Mar 2005;112(3):376-85. [Medline].

65. Ku JY, Danesh-Meyer HV, Craig JP, et al. Comparison of intraocular pressure measured by Pascal dynamic contour tonometry and Goldmann applanation tonometry. Eye. Feb 2006;20(2):191-8. [Medline].

66. Lacey J, Cate H, Broadway DC. Barriers to adherence with glaucoma medications: a qualitative research study. Eye. Apr 25 2008;[Medline].

67. Landers JA, Goldberg I, Graham SL. Detection of early visual field loss in glaucoma using frequency-doubling perimetry and short-wavelength automated perimetry. Arch Ophthalmol. Dec 2003;121(12):1705-10. [Medline].

68. Lasseck J, Jehle T, Feltgen N, et al. Comparison of intraocular tonometry using three different non-invasive tonometers in children. Graefes Arch Clin Exp Ophthalmol. Oct 2008;246(10):1463-6. [Medline].

69. Latina MA, Gulati V. Selective laser trabeculoplasty: stimulating the meshwork to mend its ways. Int Ophthalmol Clin. 2004;44(1):93-103. [Medline].

70. Latina MA, Tumbocon JA. Selective laser trabeculoplasty: a new treatment option for open angle glaucoma. Curr Opin Ophthalmol. Apr 2002;13(2):94-6. [Medline].

71. Lebrun-Julien F, Di Polo A. Molecular and cell-based approaches for neuroprotection in glaucoma. Optom Vis Sci. Jun 2008;85(6):417-24. [Medline].

72. Lee PP, Walt JW, Rosenblatt LC, et al. Association between intraocular pressure variation and glaucoma progression: data from a United States chart review. Am J Ophthalmol. Dec 2007;144(6):901-907. [Medline].

73. Leske MC, Connell AM, Wu SY, et al. Distribution of intraocular pressure. The Barbados Eye Study. Arch Ophthalmol. Aug 1997;115(8):1051-7. [Medline].

74. Levin LA, Peeples P. History of neuroprotection and rationale as a therapy for glaucoma. Am J Manag Care. Feb 2008;14(1 Suppl):S11-4. [Medline].

75. Li HK, Tang RA, Oschner K, et al. Telemedicine screening of glaucoma. Telemed J. Fall 1999;5(3):283-90. [Medline].

76. Lin SC. Endoscopic and transscleral cyclophotocoagulation for the treatment of refractory glaucoma. J Glaucoma. Apr-May 2008;17(3):238-47. [Medline].

77. Lin SC. Endoscopic and transscleral cyclophotocoagulation for the treatment of refractory glaucoma. J Glaucoma. Apr-May 2008;17(3):238-47. [Medline].

78. Lin SC, Singh K, Jampel HD, et al. Optic nerve head and retinal nerve fiber layer analysis: a report by the American Academy of Ophthalmology. Ophthalmology. Oct 2007;114(10):1937-49. [Medline].

79. Linner E. The natural course of ocular pressure in ocular hypertension. Surv Ophthalmol. Nov-Dec 1980;25(3):136-8. [Medline].

80. Lipton SA. Possible role for memantine in protecting retinal ganglion cells from glaucomatous damage. Surv Ophthalmol. Apr 2003;48 Suppl 1:S38-46. [Medline].

81. Liu J, Roberts CJ. Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. J Cataract Refract Surg. Jan 2005;31(1):146-55. [Medline].

82. Madadi P, Koren G, Freeman DJ, et al. Timolol concentrations in breast milk of a woman treated for glaucoma: calculation of neonatal exposure. J Glaucoma. Jun-Jul 2008;17(4):329-31. [Medline].

83. Medeiros FA, Zangwill LM, Bowd C, et al. Comparison of the GDx VCC scanning laser polarimeter, HRT II confocal scanning laser ophthalmoscope, and stratus OCT optical coherence tomograph for the detection of glaucoma. Arch Ophthalmol. Jun 2004;122(6):827-37. [Medline].

84. Memarzadeh F, Ying-Lai M, Azen SP, et al. Associations with intraocular pressure in Latinos: the Los Angeles Latino Eye Study. Am J Ophthalmol. Jul 2008;146(1):69-76. [Medline].

85. Migdal C. Glaucoma medical treatment: philosophy, principles and practice. Eye. Jun 2000;14 (Pt 3B):515-8. [Medline].

86. Miglior S, Casula M, Guareschi M, et al. Clinical ability of Heidelberg retinal tomograph examination to detect glaucomatous visual field changes. Ophthalmology. Sep 2001;108(9):1621-7. [Medline].

87. Milla E, Duch S, Buchacra O, et al. Poor agreement between Goldmann and Pascal tonometry in eyes with extreme pachymetry. Eye. Mar 28 2008;[Medline].

88. Minckler DS. Histology of optic nerve damage in ocular hypertension and early glaucoma. Surv Ophthalmol. Apr 1989;33:401-2; discussion 409-11. [Medline].

89. Naskar R, Dreyer EB. New horizons in neuroprotection. Surv Ophthalmol. May 2001;45 Suppl 3:S250-5; discussion S273-6. [Medline].

90. Nouri-Mahdavi K, Nikkhou K, Hoffman DC, et al. Detection of early glaucoma with optical coherence tomography (StratusOCT). J Glaucoma. Apr-May 2008;17(3):183-8. [Medline].

91. Phelps CD. The "no treatment" approach to ocular hypertension. Surv Ophthalmol. Nov-Dec 1980;25(3):175-82. [Medline].

92. Poli A, Strouthidis NG, Ho TA, et al. Analysis of HRT images: comparison of reference planes. Invest Ophthalmol Vis Sci. Sep 2008;49(9):3970-5. [Medline].

93. Quigley HA, Enger C, Katz J, et al. Risk factors for the development of glaucomatous visual field loss in ocular hypertension. Arch Ophthalmol. May 1994;112(5):644-9. [Medline].

94. Racette L, Sample PA. Short-wavelength automated perimetry. Ophthalmol Clin North Am. Jun 2003;16(2):227-36, vi-vii. [Medline].

95. Reeder CE, Franklin M, Bramley TJ. Managed care and the impact of glaucoma. Am J Manag Care. Feb 2008;14(1 Suppl):S5-S10. [Medline].

96. Reus NJ, Colen TP, Lemij HG. The prevalence of glaucomatous defects with short-wavelength automated perimetry in patients with elevated intraocular pressures. J Glaucoma. Feb 2005;14(1):26-9. [Medline].

97. Ritch R, Shields MB, Krupin T, eds. The Glaucomas. 2^nd ed. 1992.

98. Rivera JL, Bell NP, Feldman RM. Risk factors for primary open angle glaucoma progression: what we know and what we need to know. Curr Opin Ophthalmol. Mar 2008;19(2):102-6. [Medline].

99. Roizen A, Ela-Dalman N, Velez FG, et al. Surgical treatment of strabismus secondary to glaucoma drainage device. Arch Ophthalmol. Apr 2008;126(4):480-6. [Medline].

100. Sahin A, Niyaz L, Yildirim N. Comparison of the rebound tonometer with the Goldmann applanation tonometer in glaucoma patients. Clin Experiment Ophthalmol. May-Jun 2007;35(4):335-9. [Medline].

101. Schuman JS. Clinical experience with brimonidine 0.2% and timolol 0.5% in glaucoma and ocular hypertension. Surv Ophthalmol. Nov 1996;41:S27-37. [Medline].

102. Serle JB. A comparison of the safety and efficacy of twice daily brimonidine 0.2% versus betaxolol 0.25% in subjects with elevated intraocular pressure. The Brimonidine Study Group III. Surv Ophthalmol. Nov 1996;41:S39-47. [Medline].

103. Shields MB. Textbook of Glaucoma. 3^rd ed. Lippincott Williams & Wilkins; 1992.

104. Shih CY, Graff Zivin JS, Trokel SL, et al. Clinical significance of central corneal thickness in the management of glaucoma. Arch Ophthalmol. Sep 2004;122(9):1270-5. [Medline].

105. Siam GA, Gheith ME, de Barros DS, et al. Limitations of the Heidelberg Retina Tomograph. Ophthalmic Surg Lasers Imaging. May-Jun 2008;39(3):262-4. [Medline].

106. Spaeth GL. Early primary open-angle glaucoma: diagnosis and management. Preface. Int Ophthalmol Clin. Spring 1979;19(1):vii-ix. [Medline].

107. Sunaric-Megevand G, Leuenberger PM. Results of viscocanalostomy for primary open-angle glaucoma. Am J Ophthalmol. Aug 2001;132(2):221-8. [Medline].

108. Svizenska I, Dubovy P, Sulcova A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures--a short review. Pharmacol Biochem Behav. Oct 2008;90(4):501-11. [Medline].

109. Tezel G, Kolker AE, Kass MA, et al. Parapapillary chorioretinal atrophy in patients with ocular hypertension. I. An evaluation as a predictive factor for the development of glaucomatous damage. Arch Ophthalmol. Dec 1997;115(12):1503-8. [Medline].

110. Van Buskirk EM, Cioffi GA. Glaucomatous optic neuropathy. Am J Ophthalmol. Apr 15 1992;113(4):447-52. [Medline].

111. Woodward DF, Krauss AH, Chen J, et al. The pharmacology of bimatoprost (Lumigan). Surv Ophthalmol. May 2001;45 Suppl 4:S337-45. [Medline].

112. Yu DY, Su EN, Cringle SJ, et al. Comparison of the vasoactive effects of the docosanoid unoprostone and selected prostanoids on isolated perfused retinal arterioles. Invest Ophthalmol Vis Sci. Jun 2001;42(7):1499-504. [Medline].

113. Yu JY, Kahook MY, Lathrop KL, et al. The effect of probe placement and type of viscoelastic material on endoscopic cyclophotocoagulation laser energy transmission. Ophthalmic Surg Lasers Imaging. Mar-Apr 2008;39(2):133-6. [Medline].

114. Yücel YH, Gupta N. Paying attention to the cerebrovascular system in glaucoma. Can J Ophthalmol. Jun 2008;43(3):342-6. [Medline].

115. Zangwill LM, Jain S, Racette L, et al. The effect of disc size and severity of disease on the diagnostic accuracy of the Heidelberg Retina Tomograph Glaucoma Probability Score. Invest Ophthalmol Vis Sci. Jun 2007;48(6):2653-60. [Medline].

Keywords

ocular hypertension, OHT, intraocular pressure, IOP, glaucoma, primary open angle glaucoma, primary open-angle glaucoma, POAG, Ocular Hypertension Treatment Study, OHTS, high pressure inside the eye, glaucoma suspect, increased IOP, elevated IOP, high IOP, increased intraocular pressure, elevated intraocular pressure, high intraocular pressure, high eye pressure, elevated eye pressure, increased eye pressure, optic nerve, optic nerve damage, visual field defect, vision loss, blindness

Contributor Information and Disclosures

Author

Jerald A Bell, MD, Staff Physician, Department of Ophthalmology, Billings Clinic; Glaucoma Director, Leadership Council Member, Physician Advocate for Personal Service Excellence Committee
Jerald A Bell, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.

Coauthor(s)

Judie F Charlton, MD, Director - Division of Glaucoma, Professor, Department of Ophthalmology, West Virginia University
Judie F Charlton, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.

Medical Editor

Bradford Shingleton, MD, Assistant Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary
Bradford Shingleton, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Ophthalmology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Martin B Wax, MD, Clinical Professor, Department of Ophthalmology, University of Texas Southwestern Medical School; Vice President, Ophthalmology Research and Development, Head, Ophthalmology Discovery Research, Alcon Labs, Inc
Martin B Wax, MD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Society for Neuroscience
Disclosure: Alcon Labs Salary Employment

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)