Latanoprost

Know which line of treatment will work best with each glaucoma patient you encounter.

The goal in managing glaucoma is to slow or halt the progressive optic nerve damage to the point where your patient will maintain visual function for the duration of his life. Medical therapy works for roughly 80% to 90% of patients and is classically maximized before progressing to laser, then conventional surgical treatment. I'll review these three categories of treatment options in more detail.

Medical therapy

The three main drug classes used for the long-term management of primary open-angle glaucoma (POAG) include beta blockers, alpha-adrenergic agonists and prostaglandin analogs.

* Beta-adrenergic receptor antagonist (beta blockers). There was a time when beta-blockers were the gold standard of glaucoma therapy. Timolol maleate, levobunolol HCl, metipranolol and carteolol are all nonspecific beta blockers that reduce aqueous fluid production, resulting in a 22% to 26% IOP reduction.

Eyecare practitioners typically prescribed topical beta blocking solutions b.i.d., but we now know that q.i.d. dosing and the 0.25% formulation is as effective as the 0.5% solution. The most notable exception to this rule is African-American patients who may still require the 0.5% solution and b.i.d. dosing.

Ocular side effects of beta-blockers are mild and include stinging, blurred vision, allergic conjunctivitis and corneal anesthesia. Systemic side effects fall into the following three categories:

1. Cardiovascular (bradycardia, heart block and aggravation of congestive heart failure, hypercholesteremia)

2. Pulmonary (bronchospasm in asthma patients)

3. Central Nervous System (CNS) (hallucinations, insomnia, depression and impotence).

Unlike some of the other glaucoma medications in which side effects show up right away, some side effects in beta blockers don't manifest until months or years after you initiate treatment. Therefore, you need to monitor patients carefully - even those who experience no initial side effects. In addition, beta blockers experience a phenomenon known as "drift," which refers to a slow, steady rise in IOP after months or even years of treatment. As many as one-half of patients who initially respond favorably may eventually need another medication.

Many doctors now take advantage of the following new glaucoma medications.

* Alpha-Adrenergic Receptor Agonists. Brimonidine tartrate 0.15% (Alphagan P) is a selective alpha-2 agonist that decreases aqueous humor production and increases uveoscleral outflow. It incorporates a new preservative, Purite (oxycholoro complex) that's a vast improvement from the more commonly-used benzalkonium chloride (BAK).

Ocular side effects with brimonidine use include ocular irritation in nearly one-fourth of patients. Systemic side effects include dry mouth in nearly one-third of patients, fatigue and drowsiness in 5% and a few cases of headaches. In juveniles, side effects include possible CNS involvement and reports of apneic spells and cyanosis.

Brimonidine effectively lowers IOP and practitioners often dose it b.i.d., although the recommended dosing is t.i.d. The main problem with doing this is that some patients may experience a mid-afternoon, transient elevation in IOP after the morning dose wears off.

* Prostaglandin analogs. The three prostaglandin analogs available (bimatoprost, travoprost 0.004% [Travatan] and latanoprost 0.005% [Xalatan]) are potent ocular hypotensive agents that have similar side effect profiles. These medications are popular as primary glaucoma therapy because of their excellent efficacy, safety index and tolerability. They flatten the diurnal curve and achieve anywhere from 25% to 35% IOP reduction. In fact, many patients reach target pressure with q.h.s. dosing of a single agent.

* Latanoprost is a prostaglandin analog that biochemically loosens the intercellular spaces within the face of the ciliary body, enhancing uveoscleral outflow. Ocular side effects include conjunctival hyperemia, eyelash thickening, elongation of eyelashes and irreversible iris discoloration. This is usually seen in patients with mixed colored irises. This drug can cause iritis and cystoid macular edema (CME) in predisposed patients, such as those who have a history of uveitis or CME, aphakia, a YAG posterior capsulotomy or an anterior chamber IOL. Systemic side effects are rare.

* Travoprost is an FP prostanoid receptor agonist that enhances uveoscleral outflow. It has the same basic side effect profile as latanoprost, but with less incidents. During the initial Phase III clinical studies, travoprost demonstrated a disproportionate decrease of IOP in African-American patients. For this reason, many practitioners prescribe this medication as their prostaglandin of choice for this group of patients.

* Bimatoprost is a prostamide, which works either by stimulating the PGF2-alpha receptor or some other ur identified receptor, resulting in both a 35% increase in trabecular outflow facility and a 50% increase in uveoscleral outflow. The most common adverse effect is hyperemia.

Under the laser beam

Laser therapy consists of either argon laser trabeculoplasty (ALT) or selective laser trabeculoplasty (SIT).

* ALT. This is one of the most commonly performed glaucoma surgeries. The goal is to create small laser burns around the trabecular meshwork to increase aqueous fluid outflow. The practitioner performs the procedure while the patient sits at the slit lamp. In most cases, the surgeon does half the angle (180°), reserving the other half for future treatment, if necessary. He positions the laser spots at the junction of the pigmented and nonpigmented trabecular meshwork.

The Glaucoma Laser Trial established the efficacy of ALT as a primary treatment for open-angle glaucoma. Still, many O.D.s prefer ALT only in cases where medications fail to control IOP.

It typically takes four to six weeks for the full effect of ALT to manifest. Age, race and type of glaucoma are all determinants of efficacy. Patients older than 40 years typically respond better to ALT than do younger patients. The efficacy of ALT in controlling glaucoma decreases as the duration of follow up lengthens. In general, ALT controls IOP in 80% of eyes at one year, 50% at five years and 30% at 10 years. Thus, half of your patients will need additional therapy after five years and 70% to 90% will need supplemental treatment after 10 years of treatment.

Complications are usually mild and transient. They include elevated IOP, decreased vision, pain, corneal burns, hemorrhage, peripheral anterior synechiae, iritis and adverse effects on filtration surgery. Reduce the risk of a postop IOP spike by instilling one drop of an alpha adrenergic agonist one hour before and immediately after the procedure.

* SLT. Unlike ALT, which targets all cells (pigmented and non-pigmented), this new laser technique selectively targets melanin within the trabecular meshwork cells. It does so using a Q-switched frequency-doubled Nd:YAG laser. Because of this selective targeting of the laser energy, SLT doesn't cause thermal damage to surrounding tissue and the subsequent scarring to the trabecular meshwork that occurs in ALT.

Indications and contraindications for SLT are the same as those for ALT. A randomized study of patients who underwent unsuccessful ALT found that IOP reduction was better after SLT than it was after repeat ALT. Some 70% had an IOP reduction of at least 3 mmHg and an average IOP reduction of 5 mmHg to 6mmHg.

Conventional surgery

Managing glaucoma with conventional surgery consists of trabeculectomy, cyclodestructive procedures and tube shunts.

* Trabeculectomy. Filtering surgery is the most common nonlaser surgical procedure for managing glaucoma. The surgeon removes a piece of the cornea or sciera to create an alternative pathway for aqueous fluid to leave the anterior chamber. The fluid pools in a reservoir, or bleb, under the eyelid, where the episcleral venous drainage gradually absorbs it. This increased outflow facility reduces IOP. Trabeculectomy varies with the type of suture, conjunctival flap and closure technique, and whether the surgeon uses antifibrotic agents, which help prevent trabeculectomy failure due to scar formation. The two most-used antifibrotic agents are mitomycin C (MMC) and 5-fluorouracil (5-FU).

Many O.D.s refer a patient for trabeculectomy when both medical and laser therapy fail to achieve target IOP. This treatment option is most effective for cases of uncontrolled POAG, closed-angle glaucoma, exfoliation syndrome and pigmentary glaucoma. Trabeculectomy, alone or with medical therapy, has a success rate approaching 95% at two years. The long-term results are not as optimal. After five years, 60% to 80% of patients may require additional therapy or a repeat procedure. Potential complications of trabeculectomy include wound leak, flat/shallow anterior chamber, choroidal effusions, late bleb failure and formation of a Tenon cyst.

* Nonpenetrating filtering surgeries. This relatively new procedure is similar to trabeculectomy, except that the surgeon creates a thin membrane under the scleral flap without penetrating the eye. Two types of nonpenetrating surgery exist:

1. Bleb-forming surgeries include ab externo trabeculectomy (AET) and deep sclerectomy. In AET, the surgeon creates a thin membrane by excising the inner wall of Schlemm's canal and the juxtacanalicular trabecula. In deep sclerectomy, the surgeon removes corneal stroma behind the anterior trabecula and Descemet's membrane.

2. With viscocanalostomy, the surgeon removes a deep piece of scleral tissue along with part of the trabecular meshwork and anterior wall of Schlemm's canal. This allows aqueous fluid to bypass the trabecular meshwork and percolate through an intact Descemet's window.

* Tube shunts. An aqueous shunt may benefit a patient who has significant scarring from previous glaucoma surgeries or glaucoma that's resistant to other forms of treatment. In this procedure, the surgeon routes a small plastic tube from the anterior chamber of the eye to a plate inserted 10 mm behind the limbus. Aqueous fluid then drains through the tube to the top of the plate. There, the ocular blood vessels absorb the fluid, thus lowering IOP.

Tube shunts are useful in such situations as inflammatory glaucoma, angle-closure glaucoma and certain cases of chronic open-angle glaucoma when filtering surgery fails to adequately control IOP.

Shunts fall into one of two categories:

1. Shunts with valves

2. Valveless shunts.

Valved implants include the Krupin disk, the Ahmed glaucoma valve, and the white pump. Valveless shunts include the Molteno implant, the Baerveldt implant and the Schocket encircling tube.

A two-year study of outcomes after implantation of Baerveldt shunts demonstrated a success rate in open-angle glaucoma of 81%. Success rates for the Ahmed valve are about 78% with open-angle glaucoma and 83% for the Krupin disc implant.

Hypotony, with or without associated choroidal effusions, is the most common early postoperative complication of shunt implantation. Others include:

* Increased IOP, which may occur in the early postoperative period.

* Shunt patients who have crystalline lenses develop cataracts more rapidly than patients without shunts, or they experience an acceleration of growth of pre-existing cataracts. Many require cataract extraction within two years of shunt surgery.

* Strabismus occurs in 3% to 6% of shunt recipients because of rectus muscle fibrosis or elevation of the cyst, causing globe displacement.

* Later erosion of the tube and seton plate.

* Cyclodestructive procedures. Cyclocryocoagulation and cyclophotocoagulation are variations of this procedure in which the surgeon uses a special probe to freeze or photodynamically ablate part of the ciliary body. This, in turn, inhibits the production of aqueous fluid, resulting in decreased IOP. Indications for cyclocoagulation include eyes that have poor visual potential or in which filtering surgery has a high failure rate (neovascular glaucoma, aphakic and pseudophakic glaucoma) and as a therapy for end-stage glaucoma. It's generally used as a last-resort treatment surgery for glaucoma.

The full effect of treatment may take two to four weeks to manifest. If the patient needs additional treatment, wait at least one month before referring for such. However, one quadrant must remain untreated to avoid anterior segment necrosis.

Complications include postoperative pain, hypotony, inflammation of internal and external eye structures, reduced visual acuity and choroidal detachment and atrophy. Hypotony occurs in 8% to 12% of patients and may lead to the eye becoming too soft, resulting in visual impairment or loss. Also, 29% to 48% of patients may require one or more repeat treatments.

What does the future hold?

We will undoubtedly have new therapeutic agents or new combinations of medications soon. Researchers are evaluating combinations of beta blockers and prostaglandins. We'll continue to explore neuroprotection and its use in glaucoma. Two agents that may be promising are brimonidine and memantine, an NMDA-type glutamatergic channel blocker, which are being evaluated as neuroprotective agents. Early animal studies demonstrate greater preservation of visual-evoked cortical potential and enhancement of retinal ganglion cells.

BY DEEPAK GUPTA, O.D., F.A.A.O.

Stamford, Conn.

Dr. Gupta is in private practice in Stamford, Conn.. You can reach himatdeegup4919@ hotmail.com.

Copyright Boucher Communications, Inc. Nov 2004
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