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.

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

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.

Apraclonidine and anterior segment laser surgery. Comparison of 0.5% versus 1.0% apraclonidine for prevention of postoperative intraocular pressure rise.

PURPOSE: To compare the efficacy of 0.5% and 1.0% apraclonidine in preventing laser-induced intraocular pressure (IOP) elevation after trabeculoplasty, neodymium: YAG (Nd: YAG) iridotomy, and capsulotomy. METHODS: This is a prospective, masked, and randomized study of 83 patients undergoing trabeculoplasty, 62 patients undergoing iridotomy, and 57 patients undergoing capsulotomy. Surgical eyes received one drop of 0.5% or 1.0% apraclonidine immediately after surgery. RESULTS: Intraocular pressure reduced 2 hours after trabeculoplasty in the 0.5% (P = 0.028) and 1.0% (P = 0.004) groups. Intraocular pressure was higher than baseline in a greater number of eyes treated with 0.5% (12 of 39 eyes, 31%) compared with 1.0% apraclonidine (5 of 44 eyes, 11%) (P = 0.032). Intraocular pressure in eyes with a narrow chamber angle was reduced in 16 (85%) of 19 eyes treated with 0.5% and in 10 (84%) of 12 eyes treated with 1.0% apraclonidine after iridotomy. Of patients with chronic angle-closure glaucoma, IOP was similar to prelaser values in 11 (69%) of 16 eyes treated with 0.5% (P > 0.7) and 12 (80%) of 15 eyes treated with 1.0% apraclonidine (P > 0.3). In patients undergoing capsulotomy, pressure was significantly lowered in the 0.5% group (P = 0.04) but not in the 1.0% apraclonidine group. After capsulotomy, both treatment groups had similar (P > 0.3) numbers of eyes with an IOP less than baseline (83% for 0.5% apraclonidine and 81% for 1.0% apraclonidine). CONCLUSION: The single postoperative administration of 0.5% apraclonidine is as effective as the 1.0% concentration in preventing IOP elevation immediately after trabeculoplasty, iridotomy, or capsulotomy.

5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter 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.

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.

The effects of glaucoma filtering surgery on the variability of diurnal intraocular pressure.

The results of this study indicate that filtration surgery reduces the mean diurnal IOP, the range of diurnal variation, and the day-to-day variability. The effect on the range is proportionally greater than on the other two parameters. Further study will be required to determine whether this selective effect makes surgical reduction of IOP any more effective in the prevention of further glaucomatous visual field damage than other therapeutic methods that lower mean IOP to the same degree.

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 ophthalmologist's 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.

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.

Visual rehabilitation. The challenge, responsibility, and reward.

BACKGROUND: A multispecialty ophthalmology clinic created a not-for-profit foundation to establish a center for visual rehabilitation. METHODS: The Center's objective of equipping and enabling visually impaired people to lead more productive, independent, and satisfying lives by improving their remaining functional sight is performed through a four-phase program comprised of an intake interview, low vision examination, rehabilitation training, and counseling. RESULTS: Since its inception in 1986, the Center has cared for 947 females and 511 males. Although the majority of the patients examined are 61 to 90 years of age, all age groups have received care, including 41 patients younger than 10 years of age and 42 patients 91 years of age or older. CONCLUSION: The role of the ophthalmologist in the visual rehabilitation process is pivotal. The author acknowledges that most practices are unable to develop such a center. A number of suggestions are made, however, that may enable many practices to participate in the rehabilitation of their patients.

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 ophthalmologist's 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.

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.

Self-tonometry to manage patients with glaucoma and apparently controlled intraocular pressure.

We tested a self-tonometer than can be used by the patient alone to monitor intraocular pressure (IOP) in a normal environment. The instrument is safely and easily used after training. Normal subjects and patients with glaucoma who had an IOP of 22 mm Hg or less at three consecutive visits were referred for diurnal monitoring. After successful training, they received a self-tonometer and instructions to obtain five measurements daily between awakening and bedtime for three to six days. More than half the patients had one or more readings above 22 mm Hg. About half of the IOP peaks occurred at times outside of normal office hours. Interestingly, more elevated IOP readings were recorded in patients with suspected or documented progression of glaucomatous damage than in patients thought to be stable or in normal subjects. In eyes that have already sustained glaucomatous damage, the progression may be explained by the presence of previously undocumented IOP peaks. Valuable additional clinical information can be gained by diurnal IOP monitoring, and the self-tonometer is a practical tool for its measurement.

Application of a self-tonometer to home tonometry.

Although home tonometry has been advocated in the management and diagnosis of glaucoma, the lack of proper instrumentation has precluded its routine performance. We have developed a self-tonometer that can be used by the patient at home and at work and have evaluated the performance of the instrument under these conditions. The results show that reproducibility of self-tonometer measurements is +/- 1.4 mm Hg and is independent of the user. When the readings of the self-tonometer in a given individual were compared with those of the Goldmann tonometer, they varied by +/- 2.4 mm Hg. Patients who could be trained in the clinic performed well and safely on their own. An average of fewer than five attempts was necessary to obtain four readings at each time of day. Our preliminary findings obtained during home tonometry demonstrated some of the benefits of repeated diurnal curves.

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.

Treatment of intravitreal ciliary body neovascularization.

A patient who developed intravitreal ciliary body neovascularization following cyclocryotherapy for neovascular glaucoma is presented. Presenting vitreous hemorrhage limited her visual acuity to 20/200. After panretinal photocoagulation, the intravitreal ciliary body neovascularization regressed, the vitreous hemorrhage cleared, and the patient's visual acuity was 20/30. The possible pathogenesis of intravitreal ciliary body neovascularization is reviewed, and the reason for regression of the neovascular tissue is hypothesized.

Evaluation of a self tonometer for home use.

It has been repeatedly stated that home monitoring of the intraocular pressure of glaucomatous patients could be of clinical significance. However, home tonometry has not been implemented due to the lack of an appropriate instrument. We present herein an upgraded version of a home tonometer that can be used by the patient alone. When it was tested on 37 eyes of 22 glaucomatous patients, the reproducibility was 1.7 mm Hg at IOPs of 20 mm Hg. The IOP was also measured with a Goldmann applanation tonometer. The two measurements were well correlated (r = .89) and the accuracy of the home tonometer, namely the variation of the data from the regression curve, was 2.5 mm Hg. This accuracy is compared with that of conventional tonometers. Moreover, the study showed that the home tonometer yielded reliable results in the hands of a substantial portion of the potential population.

A practical venomanometer. Measurement of episcleral venous pressure and assessment of the normal range.

Glaucomatous damage develops in certain patients because of elevated episcleral venous pressure (EVP). To measure the EVP in typical clinical settings, a practical and reliable instrument is needed. We have developed such an instrument, the venomanometer, and present tests of its reproducibility. The intraobserver reproducibility was 0.7 mm Hg, and the mean difference between the readings of two observers was 0.7 +/- 1.2 mm Hg. We then used the venomanometer to study the EVP in 122 eyes of 68 normal subjects distributed in seven age groups between 10 and 80 years. The EVP did not vary with age (mean, 7.6 +/- 1.3 mm Hg). This value is compared with those obtained with other instruments.

[Morbus Coasts, Histopathological findings in an adult patient (author's transl)]. / Pathologische Befunde bei einen Erwachsenen mit Morbus Coats.

Light and electron-microscopic analysis of the enucleated eye of a 55-year-old man confirmed the diagnosis of Coats' syndrome. The histopathologic findings in this adult patient are identical to those seen in typical cases of Coats' syndrome of childhood. The characteristic thickening of vessel walls and the apparent deficiency of healthy, viable retinal vascular endothelial cells support the hypothesis that the ocular changes in this syndrome are directly related to a primary retinal vascular defect leading to abnormal permeability.