AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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

Elevated IOP is a great concern in the ocular hypertensive population because it is one of the main risk factors for glaucoma. Elevated IOP is the most studied because it is the main clinically treatable risk factor for glaucoma. Multiple theories discuss how IOP can be one of the factors that initiates glaucomatous damage in a patient. Two of the major theories include the following: (1) onset of vascular dysfunction causing ischemia to the optic nerve, and (2) mechanical dysfunction via cribriform plate compression of the axons.

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

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The initial patient interview is extremely important in the evaluation of ocular hypertension to detect frank glaucoma or other ocular diseases secondarily causing elevated IOP. Detail should be given to the following:

• Past ocular history - History of eye pain or redness; multicolored halos; headache; previous ocular disease, including cataracts, uveitis, diabetic retinopathy, and vascular occlusions; previous ocular surgery (including photocoagulation or refractive procedures); or ocular/head trauma
• 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 of the general population for ocular hypertension and POAG is similar, being most effective if targeted toward those at high risk, such as African Americans and elderly persons, especially if the screening consists of IOP measurements combined with assessment of optic nerve status.

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.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Some controversy still exists about when to treat ocular hypertension. Some of the questions regarding medical management versus observation have been answered by such studies as the OHTS.  

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

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

Drug Category: 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).

Drug Category: 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.

Drug Category: 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.

Drug Category: 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.

Drug Category: 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.

Drug Category: Beta-blocker / Alpha Agonist Combination

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

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia