2. TREATMENT GOALS. TARGET IOP*

5. Treatment goals include IOP, visual function and structural (optic disc, RNFL) outcomes and QOL.

Comment: It is uncertain whether patient reported outcomes of glaucoma can be applied in clinical practice, and whether they capture clinically meaningful progressive changes.

Concept of target IOP

The target IOP is the IOP range at which the clinician judges that the estimated rate of progression is unlikely to affect the patient’s quality of life.

Use of target IOP in clinical practice

Most clinicians use target IOP in clinical practice. The determination of a target IOP is based upon consideration of (1) the amount of glaucoma damage (according to structural and functional measures); (2) the baseline untreated IOP, i.e., the level at which the damage has occurred (ideally several readings should be available); (3) the patient life expectancy (actuarial tables may be useful), with target IOP being lower in people with longer life expectancy and target IOP higher in elderly people; (4) the rate of progression at the current IOP level (using visual fields and/or structural tests); (5) status of the fellow eye (if the fellow eye is healthy, the potential impact of glaucoma in quality of life is reduced, but if the fellow eye is blind the probability of glaucoma progression should be more vigorously minimized); and (6) family history of severe glaucoma.

It is important to acknowledge that there is a subjective component and clinical expertise appears to be an important factor in the way target IOP is determined.

There are straightforward ways of setting target IOP, while other approaches used more complex formulae trying to capture all known relevant factors mentioned above. An example of a simple initial approach would be: reduce the IOP by 30% in all newly diagnosed patients with glaucoma. Another relatively simple method would be: mild glaucoma, high teens; moderate glaucoma: mid teens; advanced glaucoma: low teens.

Target IOP should have a degree of flexibility tailored to the patient’s condition and changing ocular and general circumstances. Specifically, the risk associated with additional intervention to further lower the IOP needs to be considered when a clinician encounters an IOP outside the target. This is especially relevant when surgery is needed to further reduce the IOP, but generally speaking each treatment decision and change must balance the potential risk and benefits.

Target IOP may be more useful for some patients, e.g., those with high risk of substantial vision loss and blindness. Perhaps among patients with low risk for visual loss (e.g., ocular hypertension, mild normal tension glaucoma) the

emphasis could be on minimizing side effects of therapy rather than achieving a particular IOP.

Recording the target IOP

Most clinicians using target IOP in their clinical practice recommend recording it in the medical notes. This may be particularly useful when several clinicians are involved in patient care.

Re-evaluation of the target IOP

The definition of a target IOP is expected to change over time, depending on the patient’s circumstances and outcomes. For example, if there is rapid disease progression when the initial target IOP has been met then it would need to be revised downwards. Revision may also be considered if the fellow eye has a substantial change in visual function. Similarly, if there is a deterioration of the general health and life expectancy or if the patient has been stable for a long period, the target IOP could be raised.

Use of target IOP in clinical trials

Target IOP may be a useful outcome in glaucoma trials. For example, if two alternative interventions are compared, a possible outcome measure could be how many patients reach a pre-determined target IOP. Target IOP can also be used to set a homogenous IOP level in a group of patients and observe its effect in the progression of the disease. Target IOP has been used in several glaucoma trials (e.g., OHTS, CIGTS, CNTGS).

Limitations of using target IOP

There are important uncertainties in establishing a target IOP. One is the IOP measurement. Because of the shortand long-term variations of IOP, it is unknown whether a mean or a range of IOP should be chosen. In addition, the sub-optimal accuracy of tonometer readings and the influence of corneal biomechanical properties and thickness in IOP readings are additional limiting factors.

From the patient’s perspective, life expectancy and adherence to therapy are difficult to predict. From the disease point of view, estimation of glaucoma progression rates in clinical practice is challenging. Glaucoma progression is typically measured with visual function tests (perimetry), but current methods to diagnose progression have different sensitivities and specificities, especially in detecting relatively early progression. The added value of structural tests for detecting progression is also being investigated.

There is lack of full understanding of the effect of glaucoma on patients’ quality of life. Current patient-reported outcome measures and validated questionnaires may not capture clinically relevant changes in the condition. This is more likely to happen in earlier stages of the disease.

There is also a concern that using a fixed target IOP by inexperienced clinicians may lead to overestimate the benefits of IOP lowering and underestimation of risks associated with escalation of therapy.

Ultimately, the role of using target IOP should be evaluated in a randomized clinical trial in which one group of patients has a pre-determined target IOP level and the clinicians strive to reach it. The comparator would be a group of patients in whom there was no determination of a target IOP, or a group having different criteria for setting the target IOP. Clinical (progression of glaucoma) and patient-reported outcomes (quality of life measures) would be assessed over time. Because of the subjectivity in setting target IOP it would seem useful to evaluate the intraand inter-observer agreement in establishing target IOPs at different stages of the disease.

References

Bhorade AM, Gordon MO, Wilson B, Weinreb RN, Kass MA; Ocular Hypertension Treatment Study Group. Variability of intraocular pressure measurements in observation participants in the ocular hypertension treatment study. Ophthalmology 2009; 116: 717-724.

Damji K, Behki R, Wang L. Canadian perspectives in glaucoma management: setting target intraocular pressure range. Can J Ophthalmol 2003; 38: 189-197.

Mansberger SL, Cioffi GA. The probability of glaucoma from ocular hypertension determined by ophthalmologists in comparison to a risk calculator. J Glaucoma 2006; 15: 426-431.

Medeiros FA, Weinreb RN, Sample PA, Gomi CF, Bowd C, Crowston JG, Zangwill LM. Validation of a predictive model to estimate the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol 2005; 123: 1351-1360.

Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol 2005; 140: 598-606.

Jampel J. Target pressure in glaucoma therapy. J Glaucoma 1997; 6: 133-138.

Jampel H. Target IOP in clinical practice. In: Weinreb RN, Brandt JD, Garway-Heath D, Medeiros FA. Intraocular Pressure. Kugler Publications, Amsterdam 2007; pp 121-125.

Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence and adherence with topical glaucoma therapy. Am J Ophthalmol 2005; 140: 598-606.

Palmberg P. Evidence-based target pressures: how to choose and achieve them. Int Ophthalmol Clin 1004; 44: 1-14.

Singh K, Spaeth G, Zimmerman T, Minckler D. Target-pressure – glaucomatologists’ holy grail. Ophthalmology 2000; 107: 629-630.

Singh K, Shrivastava A. Early aggressive intraocular pressure lowering, target intraocular pressure, and a novel concept for glaucoma care. Surv Ophthalmol 2008; 53 Sup1: S33-38.

Galanopoulos A, Goldberg I. Clinical efficacy and neuroprotective effects of brimonidine in the management of glaucoma and ocular hypertension. Clin Ophthalmol 2009; 3: 117-122.

The AGIS investigators. The Advanced Glaucoma Intervention Study (AGIS) 7: The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol 2000; 130: 429-440.