keep IOP ‘under control’ and at a lower level for a longer period of time.6,8,15–17,19,30 Visual function may be better preserved with

surgery than with medical therapy but visual acuity is more immediately affected negatively.8,30 Quality of life in the long run may

be affected less negatively with surgery because fewer or no medications are likely to be necessary after a short postoperative period. Surgery is also less dependent in the long run on compliance than is medical therapy. Finally, the cost of surgery, assuming no complications, may actually be less than the cost of medication if the positive effects of the surgery last at least 8 years.

Disadvantages

Surgery is irreversible. The Rubicon is crossed, and the eye cannot be returned to its original status. Patients whose surgical intervention is successful are often quite happy to no longer require medications, but those who have a major complication are usually much more unhappy than patients who never had surgery. Significant visionand life-threatening complications can occur from surgery. Such complications include respiratory arrest and cardiovascular failure from retrobulbar anesthesia, perforation of the globe, suprachoroidal hemorrhage, maculopathy from hypotony, corneal decompensation, cataract formation, and postoperative

Table 22-1  Advantages of medical and surgical therapy

Table 22-2  Disadvantages of medical and surgical therapy

endophthalmitis.Visual distortions may occur due to induced astigmatism, cataract, or large iridectomy. Prolonged postoperative discomfort may occur from a large bleb, dellen, or surgically-induced ptosis. A large bleb or iridectomy may be a cosmetic problem for some patients. Each episode of conjunctivitis, normally a minor annoyance, becomes a major medical emergency for a patient with a filtering bleb. Cosmetic contact lens use in the presence of a filtering bleb is usually inadvisable.Yet, in the Collaborative Initial Glaucoma Treatment Study (CIGTS) study, serious complications from initial trabeculectomy were uncommon.30

In the Glaucoma Laser Trial, at least 40% of those treated initially with laser surgery needed supplemental medical therapy by 2 years after the laser treatment.19 The beneficial effect of laser treatment seems to be time limited and is frequently gone by 3–5 years after surgery. Finally, none of the prospective studies on initial laser or surgical treatment of glaucoma had follow-up beyond 5 years at the time of this writing. This is a short period compared with the lifetime nature of glaucoma to measure the true effect or actual longevity of the surgical approach. The advantages and disadvantages of medical and surgical treatment are presented in Tables 22 1 and 22-2.

Basic pharmacology

Most drugs used for glaucoma therapy are administered topically to the eye. Before discussing these drugs individually, some of the general pharmacologic principles of topical ocular treatment should be considered.

To be effective, a drug must penetrate the eye and achieve an adequate concentration at its site of action.The eye is protected by a number of mechanisms (e.g., blinking, tear flow, active transport, blood–aqueous and blood–retinal barriers), however, that limit exposure to endogenous and exogenous noxious agents. These same protective mechanisms make it difficult to reach and maintain an effective intraocular drug concentration. This problem is compounded by the structure of the eye itself, which isolates ocular tissues from the ocular and systemic blood circulation and from the ocular surface. One of the major problems in ocular therapeutics is achieving the desired effect of topical medication despite these protective mechanisms and structural obstacles (i.e., achieving an adequate concentration of drug at the site of action without creating potentially dangerous concentrations elsewhere).31

The usefulness of a drug is determined by its efficacy, potency, duration of action, and therapeutic index. Efficacy is the maximum therapeutic effect obtainable. Potency is defined as the dose producing 50% of the maximum drug effect, usually expressed as E50 or an I50. Duration of action is the length of time a drug dose exerts a biologic action. Therapeutic index is the ratio of the dose of a drug producing a toxic effect divided by the dose producing the desired effect.

The physician seeks drugs with a high therapeutic index (e.g., 10 or higher if possible). However, an acceptable therapeutic index depends on the nature of the drug and the nature of the disease being treated. Physicians use different standards when choosing