James D. Brandt

Central corneal thickness in the ocular hypertension treatment study (OHTS)

OBJECTIVE Central corneal thickness influences intraocular pressure (IOP) measurement. We examined the central corneal thickness of subjects in the Ocular Hypertension Treatment Study (OHTS) and determined if central corneal thickness is related to race. DESIGN Cross-sectional study. PARTICIPANTS One thousand three hundred one OHTS subjects with central corneal thickness measurements. INTERVENTION Central corneal thickness was determined with ultrasonic pachymeters of the same make and model at all clinical sites of the OHTS. MAIN OUTCOME MEASURES Correlation of mean central corneal thickness with race, baseline IOP, refraction, age, gender, systemic hypertension, and diabetes. RESULTS Mean central corneal thickness was 573.0 +/- 39.0 microm. Twenty-four percent of the OHTS subjects had central corneal thickness > 600 microm. Mean central corneal thickness for African American subjects (555.7 +/- 40.0 microm; n = 318) was 23 microm thinner than for white subjects (579.0 +/- 37.0 microm; P < 0.0001). Other factors associated with greater mean central corneal thickness were younger age, female gender, and diabetes. CONCLUSIONS OHTS subjects have thicker corneas than the general population. African American subjects have thinner corneas than white subjects in the study. The effect of central corneal thickness may influence the accuracy of applanation tonometry in the diagnosis, screening, and management of patients with glaucoma and ocular hypertension.

Treatment Outcomes in the Tube Versus Trabeculectomy Study After One Year of Follow-up

PURPOSE To report 5-year treatment outcomes in the Tube Versus Trabeculectomy (TVT) Study. DESIGN Multicenter randomized clinical trial. METHODS SETTINGS Seventeen clinical centers. STUDY POPULATION Patients 18 to 85 years of age who had previous trabeculectomy and/or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with intraocular pressure (IOP) ≥18 mm Hg and ≤40 mm Hg on maximum tolerated medical therapy. INTERVENTIONS Tube shunt (350-mm(2) Baerveldt glaucoma implant) or trabeculectomy with mitomycin C ([MMC]; 0.4 mg/mL for 4 minutes). MAIN OUTCOME MEASURES IOP, visual acuity, use of supplemental medical therapy, and failure (IOP >21 mm Hg or not reduced by 20%, IOP ≤5 mm Hg, reoperation for glaucoma, or loss of light perception vision). RESULTS A total of 212 eyes of 212 patients were enrolled, including 107 in the tube group and 105 in the trabeculectomy group. At 5 years, IOP (mean ± SD) was 14.4 ± 6.9 mm Hg in the tube group and 12.6 ± 5.9 mm Hg in the trabeculectomy group (P = .12). The number of glaucoma medications (mean ± SD) was 1.4 ± 1.3 in the tube group and 1.2 ± 1.5 in the trabeculectomy group (P = .23). The cumulative probability of failure during 5 years of follow-up was 29.8% in the tube group and 46.9% in the trabeculectomy group (P = .002; hazard ratio = 2.15; 95% confidence interval = 1.30 to 3.56). The rate of reoperation for glaucoma was 9% in the tube group and 29% in the trabeculectomy group (P = .025). CONCLUSIONS Tube shunt surgery had a higher success rate compared to trabeculectomy with MMC during 5 years of follow-up in the TVT Study. Both procedures were associated with similar IOP reduction and use of supplemental medical therapy at 5 years. Additional glaucoma surgery was needed more frequently after trabeculectomy with MMC than tube shunt placement.

Postoperative Complications in the Tube Versus Trabeculectomy (TVT) Study During Five Years of Follow-up

PURPOSE To describe postoperative complications encountered in the Tube Versus Trabeculectomy (TVT) Study during 5 years of follow-up. DESIGN Multicenter randomized clinical trial. METHODS SETTINGS Seventeen clinical centers. STUDY POPULATION Patients 18 to 85 years of age who had previous trabeculectomy and/or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with intraocular pressure (IOP) ≥18 mm Hg and ≤40 mm Hg on maximum tolerated medical therapy. INTERVENTIONS Tube shunt (350-mm(2) Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (MMC 0.4 mg/mL for 4 minutes). MAIN OUTCOME MEASURES Surgical complications, reoperations for complications, visual acuity, and cataract progression. RESULTS Early postoperative complications occurred in 22 patients (21%) in the tube group and 39 patients (37%) in the trabeculectomy group (P = .012). Late postoperative complications developed in 36 patients (34%) in the tube group and 38 patients (36%) in the trabeculectomy group during 5 years of follow-up (P = .81). The rate of reoperation for complications was 22% in the tube group and 18% in the trabeculectomy group (P = .29). Cataract extraction was performed in 13 phakic eyes (54%) in the tube group and 9 phakic eyes (43%) in the trabeculectomy group (P = .43). CONCLUSIONS A large number of surgical complications were observed in the TVT Study, but most were transient and self-limited. The incidence of early postoperative complications was higher following trabeculectomy with MMC than tube shunt surgery. The rates of late postoperative complications, reoperation for complications, and cataract extraction were similar with both surgical procedures after 5 years of follow-up.

Three-Year Follow-up of the Tube Versus Trabeculectomy Study

PURPOSE To report 3-year results of the Tube Versus Trabeculectomy (TVT) Study. DESIGN Multicenter randomized clinical trial. METHODS SETTING Seventeen clinical centers. STUDY POPULATION Patients 18 to 85 years of age who had previous trabeculectomy, cataract extraction with intraocular lens implantation, or both and uncontrolled glaucoma with intraocular pressure (IOP) > or =18 mm Hg and < or =40 mm Hg on maximum tolerated medical therapy. INTERVENTIONS A 350-mm(2) Baerveldt glaucoma implant or trabeculectomy with mitomycin C (MMC 0.4 mg/ml for 4 minutes). MAIN OUTCOME MEASURES IOP, visual acuity, use of supplemental medical therapy, surgical complications, and failure (IOP >21 mm Hg or not reduced by 20%, IOP < or =5 mm Hg, reoperation for glaucoma, or loss of light perception vision). RESULTS A total of 212 eyes of 212 patients were enrolled, including 107 in the tube group and 105 in the trabeculectomy group. At 3 years, IOP (mean +/- standard deviation [SD]) was 13.0 +/- 4.9 mm Hg in the tube group and 13.3 +/- 6.8 mm Hg in the trabeculectomy group (P = .78). The number of glaucoma medications (mean +/- SD) was 1.3 +/- 1.3 in the tube group and 1.0 +/- 1.5 in the trabeculectomy group (P = .30). The cumulative probability of failure during the first 3 years of follow-up was 15.1% in the tube group and 30.7% in the trabeculectomy group (P = .010; hazards ratio, 2.2; 95% confidence interval, 1.2 to 4.1). Postoperative complications developed in 42 patients (39%) in the tube group and 63 patients (60%) in the trabeculectomy group (P = .004). Surgical complications were associated with reoperation and/or loss of > or =2 Snellen lines in 24 patients (22%) in the tube group and 28 patients (27%) in the trabeculectomy group (P = .58). CONCLUSIONS Tube shunt surgery had a higher success rate compared to trabeculectomy with MMC during the first 3 years of follow-up in the TVT Study. Both procedures were associated with similar IOP reduction and use of supplemental medical therapy at 3 years. While the incidence of postoperative complications was higher following trabeculectomy with MMC relative to tube shunt surgery, most complications were transient and self-limited.

Six-month comparison of Bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure

The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.

Clinical Experience with the Baerveldt Glaucoma Drainage Implant

PURPOSE To assess clinical outcomes in patients who were treated with the Baerveldt glaucoma drainage implant. METHODS The authors performed a retrospective multicenter study of 100 patients (103 eyes) with medically uncontrollable glaucomas who underwent a one-stage implantation with either the 200-, 250-, 350-, or 500-mm2 Baerveldt implant. The authors defined surgical success as 5 mmHg less than intraocular pressure less than 22 mmHg without additional glaucoma surgery and without loss of light perception. RESULTS With a mean follow-up of 13.6 +/- 0.9 months (range, 4-37 months), 74 eyes (71.8%) had successful outcomes. Cumulative life-table success rates were 90.3% at 3 months (n = 103), 72.6% at 6 months (n = 84), and 60.3% at 24 months (n = 34). Intraocular pressure (IOP) was reduced from a mean of 38.5 +/- 1.4 mmHg with 2.2 +/- 0.1 antiglaucoma medications to 15.1 +/- 0.8 mmHg (P < 0.0005) with 0.5 +/- 0.1 antiglaucoma medications (P < 0.0005). Visual acuity was improved or remained within one line of the preoperative visual acuity in 90 eyes (87.4%). Complications occurred in 74 eyes (71.8%). A significant portion of these complications (45%) was transient, resolving without any intervention. Only 8% were serious sight-threatening complications. The most common complications included shallow anterior chamber or hypotony (32%), choroidal effusion or hemorrhage (20.4%), corneal decompensation or edema (17.5%), hyphema (14.1%), and tube obstruction (12.6%). CONCLUSION The Baerveldt implant is effective in lowering the IOP in patients with intractable glaucomas. Hypotony and other complications are common, which also have been reported in other nonvalved glaucoma drainage implants. However, the majority of these complications did not affect surgical outcome.

Comparison of once- or twice-daily bimatoprost with twice-daily timolol in patients with elevated IOP: A 3-month clinical trial

OBJECTIVE To compare the safety, tolerability, and efficacy of bimatoprost 0.03% instilled once daily or twice daily with timolol 0.5% twice daily. DESIGN Multicenter, 3-month, randomized, double-masked, interventional comparison trial. PARTICIPANTS Patients diagnosed with ocular hypertension or glaucoma (n = 596). INTERVENTION Patients received bimatoprost 0.03% ophthalmic solution once daily (8 PM, with vehicle control at 8 AM), bimatoprost 0.03% twice daily (8 AM; 8 PM), or timolol 0.5% twice daily (8 AM; 8 PM) in an uneven 2:2:1 randomization. Scheduled visits were at prestudy, baseline (day 0), weeks 2 and 6, and month 3. Intraocular pressure (IOP) was measured at 8 AM (predose), 10 AM, and 4 PM. MAIN OUTCOME MEASURES The primary outcome measure was reduction in IOP in the eye with higher IOP at baseline. Secondary outcome measures included safety variables (adverse events, ophthalmoscopy, biomicroscopy, iris pigmentation, laser-flare meter, visual acuity, visual fields, heart rate, blood pressure, blood chemistry, hematology, and urinalysis). RESULTS At month 3, the mean reduction in IOP from baseline at 8 AM was 9.16 mmHg (35.2%) with bimatoprost once daily, 7.78 mmHg (30.4%) with bimatoprost twice daily, and 6.74 mmHg (26.2%) with timolol twice daily. At all follow-up visits, mean IOP reductions were significantly greater in the bimatoprost once daily group than in the timolol group at each time point (8 AM, 10 AM, and 4 PM; P < 0.001). Twice-daily dosing of bimatoprost also provided significantly greater mean reductions in IOP than timolol at most time points but was not as effective as once-daily dosing. Bimatoprost was associated with significantly more hyperemia and eyelash growth than timolol, whereas timolol was associated with significantly more burning and stinging sensation in eyes. Overall, bimatoprost was well tolerated with few discontinuations because of adverse events. CONCLUSIONS Bimatoprost 0.03% once daily was safe and statistically superior to timolol 0.5% twice daily in lowering IOP in patients with ocular hypertension or glaucoma. Bimatoprost given once daily consistently provided IOP reductions approximately 2 to 3 mmHg greater than those provided by timolol. Once-daily dosing of bimatoprost, 0.03%, demonstrated greater IOP-lowering effect and better ocular tolerability than twice-daily dosing.

Corneal thickness in glaucoma screening, diagnosis, and management

Purpose of review Variability in central corneal thickness (CCT) is a potent confounder of most tonometry techniques, especially Goldmann applanation tonometry. The Ocular Hypertension Treatment Study (OHTS) provided important information regarding predictive factors for the eventual development of glaucoma in patients at risk of the disease. Among the most striking of the OHTS’ findings was that CCT was a powerful predictor of glaucoma risk. In this review, studies subsequent to the OHTS report will be reviewed and placed in the context of what is known about CCT and its relation with tonometry and glaucoma risk. Recent findings Several well-designed studies have since expanded on this hypothesis, confirming that CCT bears an inverse relation with the risk of developing glaucoma damage. Other investigators have confirmed the presence of racial differences in CCT and pilot studies suggest that CCT may vary systematically in different forms of glaucoma. Summary The absence of a widely-accepted algorithm for the correction of IOP measurements should not prevent the widespread adoption of pachymetry as part of the comprehensive eye exam, as knowledge of an individual’s CCT provides valuable information about their glaucoma risk.

Pigmentary dispersion syndrome induced by a posterior chamber phakic refractive lens

PURPOSE To report a case of bilateral pigmentary dispersion syndrome (PDS) induced by the implantation of posterior chamber phakic refractive lenses (PRLs). METHOD Case report. RESULTS Following bilateral implantation of posterior chamber phakic refractive lenses in 38-year-old woman, unilateral elevated intraocular pressure (IOP) developed within months that was attributable to pigment dispersion within the anterior chamber. Findings consistent with PDS included bilateral transillumination defects of the iris in areas contacting the anterior surface of the PRLs, pigment deposits on the anterior surface of the PRLs, Krukenberg spindles, and bilateral dense pigmentation of the trabecular meshwork. The patients IOP is presently under control and she has not developed glaucomatous damage. CONCLUSIONS The development of PDS in this case demonstrates that posterior chamber phakic refractive lenses can make contact with the posterior iris and induce pigment dispersion syndrome in susceptible patients.

Evidence of outer retinal changes in glaucoma patients as revealed by ultrahigh-resolution in vivo retinal imaging

Aims It is well established that glaucoma results in a thinning of the inner retina. To investigate whether the outer retina is also involved, ultrahigh-resolution retinal imaging techniques were utilised. Methods Eyes from 10 glaucoma patients (25–78 years old), were imaged using three research-grade instruments: (1) ultrahigh-resolution Fourier-domain optical coherence tomography (UHR-FD-OCT), (2) adaptive optics (AO) UHR-FD-OCT and (3) AO-flood illuminated fundus camera (AO-FC). UHR-FD-OCT and AO-UHR-FD-OCT B-scans were examined for any abnormalities in the retinal layers. On some patients, cone density measurements were made from the AO-FC en face images. Correlations between retinal structure and visual sensitivity were measured by Humphrey visual-field (VF) testing made at the corresponding retinal locations. Results All three in vivo imaging modalities revealed evidence of outer retinal changes along with the expected thinning of the inner retina in glaucomatous eyes with VF loss. AO-UHR-FD-OCT images identified the exact location of structural changes within the cone photoreceptor layer with the AO-FC en face images showing dark areas in the cone mosaic at the same retinal locations with reduced visual sensitivity. Conclusion Losses in cone density along with expected inner retinal changes were demonstrated in well-characterised glaucoma patients with VF loss.