David K. Gieser

Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma.

Purpose: To study the risk associated with diurnal intraocular pressure (IOP) variations in patients with open‐angle glaucoma. Patients and Methods: Sixty‐four patients (105 eyes) from the practices of two glaucoma specialists successfully performed home tonometry with a self‐tonometer five times a day for 5 days. All patients had open‐angle glaucoma and documented IOP below 25 mm Hg over a mean follow‐up period of 5 years. Baseline status and time to progression of visual field loss were identified from the clinical charts. The level and variability of diurnal IOP obtained using home tonometry were characterized. Risk of progression was analyzed using a nonparametric time‐to‐event model, incorporating methods for correlated outcomes. Results: Although mean home IOP and baseline office IOP were similar (16.4 ± 3.6 mm Hg and 17.6 ± 3.2 mm Hg, respectively), the average IOP range over the 5 days of home tonometry was 10.0 ± 2.9 mm Hg. Baseline office IOP had no predictive value (relative hazard, 0.98). The diurnal IOP range and the IOP range over multiple days were significant risk factors for progression, even after adjusting for office IOP, age, race, gender, and visual field damage at baseline (relative hazards [95% confidence intervals], 5.69 [1.86, 17.35] and 5.76 [2.21, 14.98]). Eighty‐eight percent of patients in the upper twenty‐fifth percentile of IOP and 57% of patients in the lower twentyfifth percentile progressed within 8 years. Conclusions: In patients with glaucoma with office IOP in the normal range, large fluctuations in diurnal IOP are a significant risk factor, independent of parameters obtained in the office. Fluctuations in IOP may be important in managing patients with glaucoma. Development of methods to control fluctuations in IOP may be warranted.

Individual variability in the diurnal intraocular pressure curve.

BACKGROUND Reduction of intraocular pressure (IOP) is a primary goal of most glaucoma treatments. However, because the IOP varies during the day, single measurements performed in an ophthalmologists office do not necessarily provide information on the peak level and fluctuation of the IOP. METHODS Home tonometry was performed to gain more information on the nature of the diurnal IOP curves and on their variability. One hundred seventy-six patients with open-angle glaucoma (OAG), 55 subjects with ocular hypertension (OHT), and 18 control individuals measured their IOP five times daily at home for 4 to 8 consecutive days using a self-tonometer. RESULTS Well-defined diurnal IOP variations were observed in all three groups with a predominance of curves with morning or mid-day maxima. Erratic IOP curves without a diurnal rhythm were present in OHT (22%) and OAG (16%) patients but not in control subjects. Differences between the curves of the two eyes of an individual were frequent in OHT (33%) and OAG (36%) patients but not in control subjects (6%). Finally, the majority of OHT (72%) and OAG (66%) patients showed a difference in their diurnal curve patterns on repeat home tonometry performed months apart. CONCLUSION The authors indicate that it is difficult to rely on one eye as a control for the other. They also indicate that changes in IOP observed in the office at different visits often may be due to a shift in the type of diurnal curve rather than to a true change in the mean IOP. Monitoring of the diurnal IOP may be necessary in some cases if the clinician relies, even partially, on the level of IOP when making a decision on patient management.

Association between Intraocular Pressure Peaks and Progression of Visual Field Loss

Little is known about the relation between diurnal variations of intraocular pressure (IOP) and prognosis for glaucomatous visual field damage. The association between apparent progressive loss of visual field and the occurrence of IOP peaks was studied. Pressure peaks were detected by a self-tonometer in the natural environment of patients with glaucoma. The study groups consisted of patients with and without a strong indication of progressive visual field losses, all with IOPs of 22 mm Hg or less obtained in the ophthalmologists office. Patients apparently undergoing progressive visual field loss were found to have significantly more frequent IOP peaks than patients with stable visual fields. A statistical evaluation indicated that, in a population with a 30% prevalence of progressive loss of visual field, 75% of the patients with peaks have progressive loss and 75% of those without peaks do not have visual field progression. Intraocular pressure peaks were thus shown to have an association with the apparent progression of vision loss independent of the mean IOP. Home tonometry appeared to be a promising tool for identifying patients at increased risk of developing visual field loss who may require intensified follow-up and an alteration in clinical management. However, the present study must be complemented by a prospective study.

A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide.

OBJECTIVE To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive medications. DESIGN A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial. PARTICIPANTS A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated. INTERVENTION After completing a washout of ocular hypotensive medications, patients were randomized to receive either the dorzolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide three times daily. MAIN OUTCOME MEASURES Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each study visit. RESULTS Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol. At morning peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the combination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences was also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group (7% vs. 1%, P = 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, and tearing eye. CONCLUSIONS After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide-timolol combination was greater than that of either of its components administered as monotherapy. The combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its individual components.

Follow-up of Angle-closure Glaucoma Suspects

One hundred twenty-nine patients thought to be at risk for developing angle-closure glaucoma underwent a baseline examination, which included gonioscopy, refraction, anterior chamber pachymetry, ultrasound biometry, and an angle-closure provocative test. Patients were then followed up with no treatment. Mean follow-up was 2.7 years with a range up to six years. Twenty-five patients developed angle closure in at least one eye during the follow-up period, but in most (17 of the 25 patients), the angle closure was nonacute (that is, no clinical signs or symptoms and no increase in intraocular pressure). None of the test factors studied showed a high sensitivity or positive predictive accuracy in detecting the eyes that later developed angle closure.

5-Fluorouracil in Initial Trabeculectomy: A Prospective, Randomized, Muldcenter Study

PURPOSE Postoperative subconjunctival 5-fluorouracil (5-FU) injections increase the success of filtration surgery in eyes with prior filtration failure or cataract removal and in eyes with secondary glaucoma. The authors evaluate the safety and benefit of adjunctive 5-FU in eyes undergoing initial trabeculectomy. METHODS Patients with phakic, uncontrolled, open-angle glaucoma who were undergoing initial trabeculectomy were prospectively assigned to the 5-FU group on the first postoperative day. Patients in this group received five 5-mg injections during 2 weeks after surgery. Patients in the control group received no injections. RESULTS Preoperative intraocular pressure (IOP) and number of antiglaucoma medications were similar in the 5-FU (n = 32) and control (n = 30) groups. Transient superficial punctate keratopathy was the only postoperative complication that occurred more frequently (P < 0.05) in the 5-FU (14 eyes) than in the control eyes (3 eyes). Patients were followed for a minimum of 1 year or until a study endpoint was reached: IOP of 21 mmHg or greater with maximum medical therapy (2 5-FU eyes and 8 control eyes; P < 0.03) or cataract removal after filtration (5 treated and 3 control eyes). At last follow-up (mean, > 20 months), IOP and the number of antiglaucoma medications were significantly lower (P < 0.02) in the 5-FU eyes (IOP, 12.0 +/- 1.3 mmHg; medications, 0.2 +/- 0.1) than in the control eyes (IOP, 16.8 +/- 1.3 mmHg; medications, 0.8 +/- 0.2). Intraocular pressure was 20 mmHg or lower in 94% of 5-FU eyes and in 73% of control eyes (P < 0.03) and 16 mmHg or lower in 84% of 5-FU eyes and in 57% of control eyes (P < 0.02). CONCLUSIONS Adjunctive 5-fluorouracil increases the rate of success, decreases the level of postoperative IOP, and reduces the need for postoperative antiglaucoma medication in eyes with open-angle glaucoma undergoing initial trabeculectomy.

Presence and Rapid Decline of Early Morning Intraocular Pressure Peaks in Glaucoma Patients

A group of nine glaucoma patients in whom home tonometry, with the self-tonometer, had previously demonstrated elevated intraocular pressure (IOP) peaks upon waking were asked to measure their IOPs when they awoke in the morning, 30 minutes later, and 1 hour later. This was repeated for 4 days and medication was taken only after the third measurement. Eight of the nine patients demonstrated a reproducible decrease in IOP ranging from 2 to 18 mmHg within 30 minutes. There are indications that the momentary IOP elevation is associated with wakening. This phenomenon raises interesting questions regarding IOP variations. It indicates that in certain cases significant IOP peaks disappear before the patient can reach the clinic and may have an effect on loss of vision.

The Use of Dorzolamide and Pilocarpine as Adjunctive Therapy to Timolol in Patients with Elevated Intraocular Pressure

PURPOSE To report the results of two studies on the use of dorzolamide as adjunctive therapy to timolol in patients with elevated intraocular pressure (IOP). In the larger study, the additive effect of dorzolamide administered twice daily also was compared with 2% pilocarpine. METHODS Both studies were parallel, randomized, double-masked, placebo-controlled comparisons. In the pilot study, 32 patients received 0.5% timolol twice daily plus either 2% dorzolamide twice daily or placebo twice daily for 8 days. In the Pilocarpine Comparison Study, 261 patients received 0.5% timolol twice daily plus 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, 2% pilocarpine four times daily, or placebo (twice daily or 4 times daily) for 2 weeks. Patients then entered a 6-month extension period and received 0.5% timolol twice daily plus either 0.7% dorzolamide twice daily, 2% dorzolamide twice daily, or 2% pilocarpine four times daily. RESULTS In the pilot study, after 8 days, additional mean percent reductions in IOP for 2% dorzolamide and placebo were 17% and 3% at morning trough and 19% and 2% at peak, respectively. In the Pilocarpine Comparison Study, after 6 months, additional mean percent reductions in IOP (morning trough) were 9%, 13%, and 10% for 0.7% dorzolamide, 2% dorzolamide, and 2% pilocarpine, respectively. Patients receiving 2% pilocarpine had the highest rate of discontinuation due to a clinical adverse experience, and the use of dorzolamide was not associated with systemic side effects commonly observed with the use of oral carbonic anhydrase inhibitors. CONCLUSION Dorzolamide twice daily was effective and well tolerated by the patients in these studies as adjunctive therapy to timolol. The larger study demonstrated that both concentrations of dorzolamide produce similar IOP-lowering effects to 2% pilocarpine.

5-Fluorouracil After Primary Combined Filtration Surgery

We examined the safety and efficacy of 5-fluorouracil in eyes with open-angle glaucoma undergoing combined cataract removal and filtration surgery. We randomly assigned one eye each of 24 patients to receive 5-fluorouracil (five injections of 5 mg during two weeks after surgery) and one eye each of 20 patients to comprise the control group. Preoperatively, the two groups had similar mean intraocular pressure (P = .8) and number of medications (P = .2). The mean intraocular pressure of the 5-fluorouracil group was 18.6 +/- 1.1 mm Hg, with 2.5 +/- 0.3 medications; that of the control group was 18.2 +/- 1.2 mm Hg, with 2.2 +/- 0.2 medications. One year postoperatively, intraocular pressure and the number of medications were significantly reduced by a similar amount in both groups of patients (5-fluorouracil, 14.2 +/- 0.7 mm Hg, 0.8 +/- 0.2 medications; controls, 14.3 +/- 0.6 mm Hg, 1.0 +/- 0.2 medications). Transient superficial punctate keratopathy occurred more frequently (P = .04) in the 5-fluorouracil group (16 of 24 eyes, 67%) than in the control group (seven of 20 eyes, 35%). In our randomized and prospective study, the adjunctive use of 5-fluorouracil did not result in improved control of intraocular pressure one year after combined surgery in eyes with open-angle glaucoma.

Laser Iridectomy in the Management of Chronic Angle-Closure Glaucoma

Nineteen eyes of 16 patients (12 men and four women ranging in age from 41 to 75 years) underwent laser peripheral iridectomy for treatment of uncontrolled chronic angle-closure glaucoma (25 to 62 mm Hg). Five of eight eyes (62.5%) with glaucomatous cupping but full visual fields attained postiridectomy intraocular pressures of less than 22 mm Hg with medical therapy. Seven of nine eyes (77.7%) that had both glaucomatous optic disk damage and visual field loss before iridectomy had controlled intraocular pressures with medical therapy after iridectomy. Because laser iridectomy is safer than trabeculectomy, we recommend that it be the initial procedure in the treatment of chronic angle-closure glaucoma.