Timolol chemical structure
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Timoptic

Timolol maleate is a non-selective beta-adrenergic receptor blocker. In its oral form (Blocadren®), it is used to treat high blood pressure and prevent heart attacks, and occasionally to prevent migraine headaches. In its opthalmic form (Timoptic®), it is used to treat open-angle and occasionally secondary glaucoma.

Side effects

The most serious possible side effects include cardiac arrhythmias and severe bronchospasms. Timolol can also lead to fainting, stroke, congestive heart failure, depression, confusion, and impotence.


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Corneal Thickness In Glaucoma Management
From Optometric Management, 1/1/04 by Gupta, Deepak

Pachymetry's role increases in importance, thanks largely to OHTS.

The corneal pachymeter has gained importance lately with many optometrists who co-manage refractive surgery patients. And thanks to the recent release of the Ocular Hypertension Treatment Study (OHTS) results, this instrument will soon become a mandatory tool for any O.D. who manages glaucoma. Read "A Review of OHTS Findings" (page 44) to learn about the findings of this study.

I'll explain why corneal thickness is important for diagnosing and managing glaucoma.

The refractive surgery factor

To study the effects of excimer laser photorefractive keratectomy (PRK) on IOP, Chatterjee, et al., compared IOP taken by noncontact tonometry in 1,320 eyes following PRK with the IOP in the fellow eyes immediately before undergoing PRK. They found consistently lower pressures in the treated eyes.

The amount of IOP lowering was correlated with the extent of myopia treated, which implies that it was not the procedure itself that lowered the IOP - rather, it was a thinning of the cornea that was leading to a lowering of the IOP measurements. Based on this and other studies, many researchers are continuing investigations of the impact of the variability in corneal thickness among the general population on IOP measurement.

Reviewing the literature

A number of studies in the 1970s investigated the relationship between central corneal thickness and IOP measurement. In a manometric study, researchers demonstrated that the average error in IOP readings was 0.71 mmHg for a 10-µm deviation from the normal central corneal thickness of 520 pm. Others have found a similar relationship between IOP and central corneal thickness.

A study at the University of Nebraska found that patients who have thicker corneas may have less IOP reduction with medication than those who have thinner corneas. The retrospective study included 109 patients who had ocular hypertension and 97 patients who had normal IOP and no ocular disease. The researchers measured baseline central corneal thickness by slit lamp pachymetry and IOP by pneumatonometry. They divided the subjects into the Thin Cornea Group (central corneal thicknesses of 540 µm).

The researchers started the patients in the thin cornea group on a unilateral treatment with either latanoprost 0.005% (Xalatan), dorzolamide HCl 2.0% (Trusopt), brimonidine 0.2% (Alphagan), apraclonidine 0.5% (Iopidine), timolol maleate 0.5% (Timoptic), pilocarpine HCl 2.0% (Pilocar) or unoprostone 0.15% (Rescula). The fellow eyes received a vehicle.

The researchers found that IOPs were significantly lower in the Thin Cornea Group (16.3 mmHg ±2.6 mmHg) than in the Thick Cornea Group (17.4 mmHg ±2.8) and lower in the treated eyes versus the control eyes within each group. The treated eyes showed a positive correlation between IOP and central corneal thickness after treatment.

One of the possibilities the researchers proposed for this correlation between central corneal thickness and IOP response to medical therapy is that corneal thickness may affect bioavailability of topical drugs to their target tissues.

Recasting the numbers

In a study analyzing central corneal thickness among glaucoma patients and normal patients, those who didn't have glaucoma demonstrated a mean central cornea! thickness of 554 µm, while patients who had open-angle glaucoma had a mean central corneal thickness of 550 µm. Patients who had normal-tension glaucoma had a mean central corneal thickness of 514 µm, and those who had ocular hypertension had a mean central corneal thickness of 580 µm.

If we correct the maximum measured IOP in these patients using one of the IOP/central corneal thickness algorithms, then we'd have to reclassify 44% of patients originally diagnosed as having normal-tension glaucoma as actually having primary open-angle glaucoma, and 33% of patients diagnosed with ocular hypertension as normal.

Explaining racial differences

Dr. Argus reported in 1995 that black male veterans tend to have thinner central corneal thickness values than their white counterparts. These racial differences in central corneal thickness may help to explain the more advanced progression of glaucomatous visual field loss at a relatively lower measured IOP among blacks compared to whites.

What does this all mean?

We all know that Goldmann tonometry measures IOP through a series of calculations based on the force required to applanate the central 3.06 mm of the eye. In simple terms, the force required to do this is a combination of opposition to IOP in addition to the force needed to bend the cornea. Therefore, the thicker the cornea, the more force will be required to bend it; the thinner the cornea, the less force will be needed.

Thus, any significant deviations from the normal central corneal thickness of roughly 520 microns (what Goldmann tonometry is calibrated for) results in a potentially erroneous measurement of IOP. And, because IOP remains an integral part of glaucoma diagnosis and management, corneal thickness becomes an integral part of managing glaucoma as well.

Playing a dual role

The role of corneal thickness in glaucoma is basically divided into two parts.

* Part one. This part involves recalculating IOP in patients who have undergone refractive surgery to compensate for this change in corneal thickness. This is a simple algorithm in which you input numbers and get the patient's true IOP reading. To date many studies are researching the appropriate correction factors.

One such study found that a 70-µm change in central corneal thickness corresponded to approximately 5 mmHg of IOP difference. Another determined that a 100-µm change in central corneal thickness corresponded to a 2-mmHg difference in IOP. A recent meta-analysis calculated a correction factor of 2.5 mmHg for each 50 µm change in central corneal thickness.

* Part two. The more complicated and more important aspect of corneal pachymetry and its role in glaucoma is the newfound realization that corneal thickness is an independent risk factor for the development of glaucoma. This means that any patient who has glaucoma or who is suspected of having glaucoma should have a practitioner measure his corneal thickness.

Patients who have thinner-than-normal corneas will require a more careful evaluation, especially in the presence of elevated IOP. One reason for this is that the results from OHTS tell us that the patient who has thin corneas ( 24 mmHg) is at significant risk of developing glaucoma. Thus, a patient who has a measured IOP of 27 mmHg and corneal thickness of 640µm might be less likely to develop glaucoma than a patient who has a measured IOP of 17 mmHg and a corneal thickness of 430µm.

This means that many patients who are currently classified as having ocular hypertension will be reclassified as either glaucoma suspect or normal after ad justing for central corneal thickness.

More change to come

Corneal thickness will undoubtedly change management strategies for glaucoma as well. Current studies indicate that it's more difficult to lower IOP in patients who have a thick cornea than it is to lower the same measurement in patients who have thin corneas.

As we research this variable further, I think the day will come when we set target pressure, taking into consideration the usual risk factors which we have also considered, but also corneal thickness. Because thinner corneas seem to be more suspectible to glaucoma development, we'll aim for lower target IOPs in those patients. Also, recalculating IOPs may aid us in helping patients who appear to demonstrate glaucomatous visual field progression despite their IOPs being at target levels.

References are available upon request.

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

Stamford, Conn.

Dr. Gupta practices full-scope primary care optometry at Stamford Ophthalmology. You can reach him at deegup4919@hotmail.com.

Copyright Boucher Communications, Inc. Jan 2004
Provided by ProQuest Information and Learning Company. All rights Reserved

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