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Tailoring medical, laser and surgical therapy

ByKuldev Singh, MD, MPH

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To tailor glaucoma therapy to an individual patient, ophthalmologists must follow five steps. First, the patient must be diagnosed and the ophthalmologist must identify the stage of disease at the time of diagnosis. Second, the risk of vision loss at the time of diagnosis must be determined. Although it is optimal to have an idea of the rate of disease progression, such an assessment is difficult if not impossible on the initial visit and, further, is not absolutely necessary. More important is an assessment of the risk of functional vision loss over the patient’s lifetime, which is also difficult to estimate.

Third, the ophthalmologist should set a target for success and initiate treatment. The target will differ among patients. For some patients, it may be a range of IOPs, while for others there may not be a target IOP, but rather a goal of reducing risk with safe therapy.

After setting a treatment goal that may or may not involve an arbitrary IOP target, the next step is to attempt to reach that goal. Finally, the physician should attempt to modify therapy when the target goal cannot be reached or when the patient is doing worse than initially expected with regard to either visual preservation or side effects of therapy.

Continuum and diagnosis

Glaucoma is a continuum of disease, and the earliest stages of the disease are generally undetectable. At diagnosis, many patients will present with intermediate-stage glaucoma.

The glaucoma continuum can be separated into three categories: patients with undetectable disease, those with asymptomatic disease and patients with symptomatic disease (Figure 1).

Debate exists within the glaucoma community regarding whether or not early diagnosis is critical. Although some may postulate that early diagnosis has the potential to lead to overtreatment, it is difficult to argue against the value of early diagnosis.

By diagnosing glaucoma in its earliest stages, one can only improve patient awareness of the disease process. In addition, early diagnosis gives the ophthalmologist more time to sufficiently monitor the patient such that one can assess the rate of disease progression. Insufficient treatment is likely less problematic in the early stage as compared with the late stage of the disease; early diagnosis provides the practitioner with the luxury of time when it comes to adjusting therapy.

While conclusive evidence of an association between early diagnosis and the prevention of glaucoma-associated vision loss is lacking, the prevailing opinion in the glaucoma community remains that identifying patients earlier along the glaucoma continuum reduces the likelihood of vision loss and blindness.

Risk of vision loss

Risk factors for lifetime vision loss from glaucoma include elevated IOP, age, race, family history, disease severity and the patient’s overall health.

As patients age, they are more likely to have optic nerve damage at any given IOP level. Advanced age, however, is associated with a shorter life expectancy, all other factors being equal. On average, elderly patients with early-stage glaucoma will not have as much time to progress along the glaucoma continuum as patients diagnosed at a younger age.

In my opinion, disease severity at the time of diagnosis is an important prognostic indicator regarding lifetime risk of vision loss from glaucoma. If patients are seen in the early stages of the continuum, progression to blindness is rare, especially under the care of an ophthalmologist. In contrast, many patients who present at later stages of the disease do poorly, even when treated appropriately.

Target IOP and progression velocity

Two definitions exist for the concept of target IOP. The American Academy of Ophthalmology defines target IOP as a range of IOP adequate to stop progressive pressure-induced injury.¹ This definition implies that glaucoma progression can be completely halted and that treatment providers should continue to treat until the patient reaches an IOP range at which the disease process stops.

A more practical definition of target IOP might be the level of IOP at which the marginal benefit of further pressure lowering is likely outweighed by the risk associated with therapy required to achieve such lowering. The drawback with the concept of target IOP, regardless of the definition, is that it is, at best, an educated guess. Although most practitioners have an idea of what target IOP range they would like to achieve in each patient, the necessity of choosing a target IOP on the first visit is debated.² A physician generally gets a better idea of what the optimal target range should be by following the patient over time. Target IOP should be adjusted throughout a patient’s therapeutic course based on the patient’s individual response and risk factors. Treatment decisions should be made with regard to limits of the various treatments, both medical and surgical.²

Several large clinical trials have shown that lowering IOP is beneficial regardless of the stage of the continuum at which the patient presents.^3-8 Each of these studies did not examine patients at the same disease stage and also used different IOP end points. In spite of the differences, the studies had a common finding: The lower the IOP, the less likely patients are to progress through the stages of the continuum.

Velocity of progression may be difficult to assess in patients, particularly when ophthalmologists rely only on visual fields, which can show significant variability (Figure 2). Without examining the optic nerve, an ophthalmologist may miss nerve changes in patients with normal or minimally affected visual fields. This is not to say that detectable nerve damage always precedes detectable visual field progression. At the cellular level, structural damage and functional loss is occurring simultaneously and the ability to detect one vs. the other first depends upon several factors such as the skill of the examiner, the tools he or she uses and patient characteristics.

Adjusting therapy

Without evidence of glaucomatous progression, an ophthalmologist generally should not alter therapy, but, in rare situations, one should consider reducing therapy, especially in the instance when side effects are noted. Automatic adjustments to glaucoma therapy are not required every time an ophthalmologist notes progression. In some instances, the disease state is mild and the velocity of progression slow such that the likelihood of functional vision loss in a patient’s lifetime is small.

Generally, an ophthalmologist should consider advancing therapy for patients with rapid progression of glaucoma, as well as for patients with moderate or advanced disease who are progressing slowly. For high-risk patients with rapid progression, an ophthalmologist should not feel compelled to try every possible glaucoma medication combination.

In contrast, surgery is not needed for low-risk patients even when IOP rises above the target IOP set at the time of diagnosis. For example, in a patient with ocular hypertension for whom the target IOP was 21 mm Hg or less when therapy was initiated, one should not proceed to filtration surgery even if the IOP remains in the mid or even high 20s on three glaucoma medications, in my opinion. Although one can argue the pros and cons of medical therapy for a patient without glaucoma but with a high risk of developing the disease, such a patient should not be treated with a glaucoma surgical procedure. Laser trabeculoplasty is an excellent choice for patients with early or moderate glaucoma who are at low or intermediate risk of long-term vision loss, particularly in cases where medical therapy has not resulted in adequate IOP lowering.

In conclusion, therapy should be tailored to the patient based on the severity of glaucoma at the time of diagnosis and the risk of disease progression to a functional deficit over a patient’s lifetime, keeping in mind that the risks and side effects of therapy should not be greater than the likely potential harm from the disease itself.

References

1. The American Academy of Ophthalmology Glaucoma Panel. Primary open-angle glaucoma preferred practice pattern. Available at www.aao.org. Last accessed Feb. 28, 2006.
2. Singh K, Spaeth G, Zimmerman T, Minckler D. Target pressure — glaucomatologists’ holey grail. Ophthalmology. 2000;107:629-630.
3. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Study: Baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:714-720.
4. Anderson DR, for the Normal Tension Glaucoma Study. Collaborative normal tension glaucoma study. Curr Opin Ophthalmol. 2003;14:86-90. Review.
5. Musch DC, Lichter PR, Guire KE, Standardi CL. The Collaborative Initial Glaucoma Treatment Study: Study design, methods and baseline characteristics of enrolled patients. Ophthalmology. 1999;106:653-662.
6. 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.
7. The European Glaucoma Prevention Study Group. Results of the European Glaucoma Prevention Study. Ophthalmology. 2005;112:366-375.
8. Heijil A, Leske C, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: Results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120:1268-1279.