August 23, 2011
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Choosing Initial Glaucoma Therapy

Medications and surgical interventions are both effective options for treating glaucoma. In 2001, the Collaborative Initial Glaucoma Treatment Study showed that the visual field is similarly stabilized with either initial surgery or initial aggressive medical treatment.1 However, surgery was associated with a higher frequency of vision loss from cataract formation.1 Physicians and patients in the United States usually choose medication as the initial treatment for glaucoma.2,3

Current guidelines for medical therapy suggest lowering intraocular pressure by at least 25% in patients who have ocular hypertension and moderate to high risk for developing glaucoma.3-5 For patients with early to moderate glaucoma, ophthalmologists should aim for at least a 30% reduction in IOP and a 40% reduction or more in cases of severe disease.4,6 More aggressive treatment is warranted for patients with a long life expectancy, a greater number of risk factors or a vascular component to their disease.

Efficacy and Dosing

Once-daily prostaglandin analogues are the most effective drugs for treating primary open-angle glaucoma and ocular hypertension, on average decreasing IOP by approximately 30%7-12 and exhibiting comparable results.13 The IOP effects of bimatoprost 0.01% and 0.03% are equivalent.14 Both persistence and adherence are better with prostaglandins than with other classes.15

Short-term16-21 and long-term fluctuations in IOP have been implicated in progressive glaucomatous damage22 and progressive visual field deterioration.21-24 However, one trial did not find IOP fluctuation to be an independent risk factor for progression; another did not show an independent relationship between IOP fluctuation and development of glaucoma; and a third found that long-term IOP fluctuation was associated with visual field progression only in patients with low mean IOP.24

Until we know the true effect of IOP fluctuation, aiming for the least amount of circadian variation in IOP is best accomplished with prostaglandin analogues.21,25 Evening dosing is generally preferred, given the slow onset and peak effect at 8 to 12 hours after instillation.26 Nevertheless, the difference between morning and evening dosing is not significant,27 and morning dosing may improve adherence.

Beta-blockers have little nocturnal therapeutic effect on IOP and should be dosed in the morning.21,26 Concurrent use of systemic beta-blockers decreases the IOP-lowering effect of topical beta-blockers while compounding systemic side effects.28,29

When used as monotherapy brimonidine should be instilled 3 times a day.30,31 Brimonidine 0.1% and 0.15% with Purite and 0.2% with BAK are equivalent in lowering IOP.32 Brinzolamide and dorzolamide demonstrate a similar effect on IOP33,34 and should be instilled 3 times a day as monotherapy, twice a day as adjunctive therapy.33,34 Brinzolamide is buffered at a more neutral pH than dorzolamide and requires shaking before instillation.33

Side Effects

Prostaglandin analogues have been associated with possibly permanent iris pigment changes; darkening of periorbital skin and eyelash changes may be reversible.35 Prostaglandins also appear to be associated with cystoid macular edema, iritis and reactivation of ocular herpes simplex keratitis.36-38 Other side effects of include periorbital fat atrophy associated with deepening of the upper eyelid sulcus without change in palpebral fissure,39 loss of fullness in the lower eyelid, involution of dermatochalasis and a relative enophthalmos with monocular treatment.40,41 These effects may be more prominent in Asians, who tend to have relatively full upper lid sulcus.42 These side effects seem to be reversible (Figure).39,41,43

Periorbital Changes after Prostaglandin Analogue
Figure
A: At presentation, a 66-year-old man treated with bimatoprost 0.03% in the right eye daily. Note the prominent right upper eyelid sulcus (long arrow), the absence of dermatochalasis in the right upper eyelid, and the relative absence of the right lower eyelid fullness (short arrow). B: Six months after discontinuation of topical bimatoprost, he assumed a more symmetric appearance with increased fullness of the right upper eyelid sulcus (B, upper arrow), and emergence of some lower eyelid convexity (B, lower arrow).
Source: Filippopoulos T. Ophthal Plast Reconstr Surg. 2008;24:302–307.


Click here for a larger view of this image.

Brimonidine can cause fatigue and drowsiness, and can cause somnolence in infants.44

Cost

In terms of retail cost, nonselective beta-blockers are the most inexpensive class of glaucoma drugs.45 However, the less obvious cost-per-dose of medication depends on volume of liquid in the bottle and drop size,46 both of which vary by medication and brand.45-47

Another way to measure cost is cost effectiveness or mm Hg reduction in IOP per individual drop.48,49 Prostaglandin analogues lower IOP more than other classes of medication3,49,51 and have a higher number of patients with acceptable IOP on monotherapy.51 The real cost of treatment may be less than 5% between prostaglandin analogues and beta-blockers.49 Helping patients understand these values may decrease resistance to paying a higher retail cost.

Generic medications may be a cost-saving option, especially now with a generic prostaglandin analogue (latanoprost). However, differences in pH and inactive ingredients may affect therapeutic equivalence, and packaging and drop-size differences may result in less usable medication, negating a cheaper retail cost.52 To prevent generic substitution for brand-name prescriptions, a handwritten “dispense as written” or similar phrase is required by many states; a simple check box to that effect is not sufficient.53-55 In addition to generic substitution, patients can obtain medications online with—and sometimes without—a valid prescription.56,57 Prescribing brimonidine requires specificity: The 0.01% formulation is available only from Allergan;58 0.15% with Purite is manufactured by Allergan, and a generic equivalent, brimonidine 0.15% with Polyquad, is produced by Falcon;58-60 the 0.2% formulation has multiple generic versions.

Pharmaceutical patient-assistance programs can help some patients receive their medications, but they should note that the higher the medication formulary tier, the higher the copay.61

Figure
Source: Gaynes BI, et al. J Ocul Pharmacol Ther. 2007;23:196-201.


References

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