Target Intraocular Pressure

After the decision to treat has been made, a treatment goal must be set. Glaucoma medications lower IOP, but how low should the IOP be? Target IOP is defined as the IOP that is expected to confer optic nerve stability in a patient with glaucoma. Once the target IOP is reached, ideally the rate of ganglion cell loss is lowered to that of age-matched controls or it will be lowered to a rate at which patients will not become visually handicapped during their lifetime.

Name

Study Design

Results

Scottish Glaucoma Trial

Moorfields Primary Treatment Trial21

Glaucoma Laser Trial

Glaucoma Laser Trial Follow-up Study23

Fluorouracil Filtering Surgery Study29

Advanced Glaucoma Intervention Study

(AGIS)32-34

116 newly diagnosed POAG patients randomized to medical therapy vs. trabeculectomy

168 newly diagnosed POAG patients randomized to medical therapy, trabeculoplasty, and trabeculectomy

271 newly diagnosed POAG patients randomized to medical therapy vs. laser trabeculoplasty

203 patients from Glaucoma Laser Trial followed for 6 to 9 years

213 high-risk patients undergoing trabeculectomy randomized between postoperative 5-FU or no antimetabolite

591 patients with medically uncontrolled glaucoma randomized to trabeculectomy or trabeculoplasty

Collaborative Normal-Tension Glaucoma Study

(CNTGS)14,37,38

230 NTG patients observed until increased risk of progression, and randomized to observation or 30% IOP lowering

Trabeculectomy lowered IOP more and had less visual field loss Caveat: limited medication options

Trabeculectomy lowered IOP more and had less visual field loss Caveat: limited medications and 98% surgical success at 5 years

Initial trabeculoplasty at least as effective as initial timolol Caveat: limited medication options

Confirmed Glaucoma Laser Trial findings with extended follow-up Caveat: limited medication options

5-FU reduced 5 year failure rate from 74% to 51% Caveat: increased risk of bleb leak

African Americans had better results with trabeculoplasty as initial treatment, while Caucasians had better results with trabeculectomy Mean IOP of 12.3 mm Hg limits glaucoma progression Caveat: retrospective analysis

Lowering IOP in NTG by 30% reduced the risk of progression from 35% to 12% Caveat: only after effect of cataract is removed; 50% of patients with no treatment did not progress over 5 years

(continued)

188 Glaucoma Medical Therapy Table 10.1 (Continued)

Name

Study Design

Results

Ocular Hypertension

Treatment Study (OHTS)9,15

Early Manifest Glaucoma Trial (EMGT)16,40

European Glaucoma

Prevention Study (EGPS)43

1,637 ocular hypertensive patients randomized to medical treatment to lower IOP by 20% or observation

255 glaucoma patients randomized to observation or treatment with betaxolol and trabeculoplasty

Collaborative Initial Glaucoma Treatment Study (CIGTS)41,42

607 newly diagnosed glaucoma patients randomized to medical treatment vs. trabeculectomy

1,077 ocular hypertensive patients randomized to medical therapy with dorzolamide or placebo (dorzolamide vehicle)

Lowering IOP by 20% reduced risk of glaucoma development in ocular hypertensive patients from 9.5% to 4.4% over 5 years Thinner central corneal thickness is a risk factor for glaucoma development

Lowering IOP 25% reduced risk of glaucoma progression from 62% to 45% over 6 years Caveat: 45% of treated patients still progressed; may need lower IOP target

Lowering IOP with medication was as effective as lowering IOP with trabeculectomy in limiting glaucoma progression Caveat: IOP was lowered more in surgical group 48% vs. 35%

Medical therapy lowered IOP by 22% and placebo lowered IOP by 19% No difference in rates of glaucoma development Caveat: data do not match with other trials, and placebo effect is unexpectedly high

There is no well-defined method of choosing a target IOP. Several theories are inherent in setting a target IOP. It is generally believed that damaged optic nerves require greater IOP reduction. Dr. Morton Grant summarized this concept as follows: ''[T]he worse the initial condition of the eye, the lower the tension needs to be to prevent further vision loss or blindness.''45 Visual field loss and optic nerve cupping are the best indicators of such damage. Future glaucomatous visual field loss can be correlated with the current degree of field loss and with the current IOP compared with the IOP at which visual field loss is believed to have occurred.46

Finally, because IOP is the only currently addressable risk factor for the progression of glaucoma, individuals with additional risk factors may benefit from greater IOP reduction.47

In its 2005 Primary Open-Angle Glaucoma Preferred Practice Pattern,5 the AAO recommends that the initial target IOP be at least 20% below that of pretreatment levels, assuming that damage occurred at those pressure levels. The AAO further recommends an adjustment downward of target IOP based on responses to the following questions:

1. How severe is the existing optic nerve damage?

3. How rapidly has the optic nerve damage occurred?

4. How many additional risk factors are present?

One method of grading the severity of damage recommended by the AAO is as follows:

1. Mild: Characteristic optic nerve abnormalities are consistent with glaucoma, but the visual field is normal.

2. Moderate: Visual field abnormalities exist in one hemifield and are not within 5° of fixation.

3. Severe: Visual field abnormalities exist in both hemifields or visual field loss is within 5° of fixation.

This grading system assists in quantifying the degree of preexisting glaucomatous damage while selecting a target IOP. With mild damage, an initial goal of 20% reduction in IOP is reasonable. A 30% reduction with moderate damage and 35% to 40% reduction with severe damage may be more appropriate. With the potential of "preperimetric" glaucoma being identified with newer nerve fiber layer analyzers we may begin to identify patients with more mild glaucoma. Currently, most glaucoma diagnoses are made in conjunction with visual field loss and would, by definition, be at least moderate requiring an initial target IOP reduction of at least 30%. This fits nicely with EMGT and CIGTS data, which indicate that lower target pressures may be more appropriate. With very advanced disease and near-total optic nerve cupping, most glaucoma specialists believe the IOP should be maintained below 15mmHg. Some glaucoma specialists are recommending an upper limit in the single digits to low teens for these advanced cases. AGIS data showing average visual field stability in patients with IOPs consistently below 18 mm Hg, with a mean IOP of 12.3 mm Hg, support this position.35

Once a target IOP has been selected, it is important to remember that it is not a fixed target, but the target can be adjusted according to the patient's clinical course. If the patient continues to show optic nerve or visual field deterioration despite consistent maintenance at the target IOP and adherence to the medical regimen, it would be reasonable to further reduce the target IOP. Similarly, if visual fields and optic nerves have remained stable at the target IOP for a long time, the clinician could consider reducing medications and temporarily raising the target IOP.

Lower target pressures are associated with increased financial costs and treatment-related side effects. Without the potential downside to treatment, a very low target IOP would be selected for all glaucoma patients. The target IOP can also be adjusted depending on the ease with which it can be reached. Some patients may easily reach their target IOP on one medication used only once a day. If further IOP lowering can be achieved by adding another drop, which the patients tolerate well and are willing to take, it may be reasonable to aim for an IOP lower than the target IOP. On the other hand, if patients are having difficulty reaching the target IOP despite multiple medications and laser treatment, the next step may be surgery. If patients cannot increase their medical regimen and if they are hesitant to undergo surgery, the importance of reaching the IOP goal must be reassessed. If the potential benefit of reaching the target IOP is outweighed by the potential risks of further treatment, IOP greater than the target IOP may be acceptable. However, these patients must be observed closely to detect evidence of progression.

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