Donald L. Budenz

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.

Macular Ganglion Cell–Inner Plexiform Layer: Automated Detection and Thickness Reproducibility with Spectral Domain–Optical Coherence Tomography in Glaucoma

PURPOSE To demonstrate the capability of SD-OCT to measure macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness and to assess its reproducibility in glaucomatous eyes. METHODS Fifty-one glaucomatous eyes (26 mild, 11 moderate, 14 severe) of 51 patients underwent macular scanning using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) macula 200×200 acquisition protocol. Five scans were obtained on 5 days within 2 months. The ganglion cell analysis (GCA) algorithm was used to detect the macular GCIPL and to measure the thickness of the overall average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL. The reproducibility of the measurements was evaluated with intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and test-retest standard deviations (TRTSDs). RESULTS Segmentation and measurement of GCIPL thickness were successful in 50 of 51 subjects. All ICCs ranged between 0.94 and 0.98, but ICCs for average and superior GCIPL parameters (0.97-0.98) were slightly higher than for inferior GCIPL parameters (0.94-0.97). All COVs were <5%, with 1.8% for average GCIPL and COVs for superior GCIPL parameters (2.2%-3.0%) slightly lower than those for inferior GCIPL parameters (2.5%-3.6%). The TRTSD was lowest for average GCIPL (1.16 μm) and varied from 1.43 to 2.15 μm for sectoral GCIPL CONCLUSIONS: The Cirrus HD-OCT GCA algorithm can successfully segment macular GCIPL and measure GCIPL thickness with excellent intervisit reproducibility. Longitudinal monitoring of GCIPL thickness may be possible with Cirrus HD-OCT for assessing glaucoma progression.

Glaucoma Diagnostic Accuracy of Ganglion Cell–Inner Plexiform Layer Thickness: Comparison with Nerve Fiber Layer and Optic Nerve Head

PURPOSE To determine the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with the Cirrus high-definition optical coherence tomography (HD-OCT) ganglion cell analysis (GCA) algorithm (Carl Zeiss Meditec, Dublin, CA) to discriminate normal eyes and eyes with early glaucoma and to compare it with that of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements. DESIGN Evaluation of diagnostic test or technology. PARTICIPANTS Fifty-eight patients with early glaucoma and 99 age-matched normal subjects. METHODS Macular GCIPL and peripapillary RNFL thicknesses and ONH parameters were measured in each participant, and their diagnostic abilities were compared. MAIN OUTCOME MEASURES Area under the curve (AUC) of the receiver operating characteristic. RESULTS The GCIPL parameters with the best AUCs were the minimum (0.959), inferotemporal (0.956), average (0.935), superotemporal (0.919), and inferior sector (0.918). There were no significant differences between these AUCs and those of inferior quadrant (0.939), average (0.936), and superior quadrant RNFL (0.933); vertical cup-to-disc diameter ratio (0.962); cup-to-disc area ratio (0.933); and rim area (0.910), all P>0.05. CONCLUSIONS The ability of macular GCIPL parameters to discriminate normal eyes and eyes with early glaucoma is high and comparable to that of the best peripapillary RNFL and ONH parameters. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

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.

Common Variants at 9p21 and 8q22 Are Associated with Increased Susceptibility to Optic Nerve Degeneration in Glaucoma

Optic nerve degeneration caused by glaucoma is a leading cause of blindness worldwide. Patients affected by the normal-pressure form of glaucoma are more likely to harbor risk alleles for glaucoma-related optic nerve disease. We have performed a meta-analysis of two independent genome-wide association studies for primary open angle glaucoma (POAG) followed by a normal-pressure glaucoma (NPG, defined by intraocular pressure (IOP) less than 22 mmHg) subgroup analysis. The single-nucleotide polymorphisms that showed the most significant associations were tested for association with a second form of glaucoma, exfoliation-syndrome glaucoma. The overall meta-analysis of the GLAUGEN and NEIGHBOR dataset results (3,146 cases and 3,487 controls) identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR = 0.69 [95%CI 0.63–0.75], p = 1.86×10−18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR = 1.32 [95%CI 1.21–1.43], p = 3.87×10−11). In sub-group analysis two loci were significantly associated with NPG: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR = 0.58 [95% CI 0.50–0.67], p = 1.17×10−12) and a probable regulatory region on 8q22 (rs284489 [G], OR = 0.62 [95% CI 0.53–0.72], p = 8.88×10−10). Both NPG loci were also nominally associated with a second type of glaucoma, exfoliation syndrome glaucoma (rs2157719 [G], OR = 0.59 [95% CI 0.41–0.87], p = 0.004 and rs284489 [G], OR = 0.76 [95% CI 0.54–1.06], p = 0.021), suggesting that these loci might contribute more generally to optic nerve degeneration in glaucoma. Because both loci influence transforming growth factor beta (TGF-beta) signaling, we performed a genomic pathway analysis that showed an association between the TGF-beta pathway and NPG (permuted p = 0.009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma.

Comparison of Retinal Nerve Fiber Layer Measurements Using Time Domain and Spectral Domain Optical Coherent Tomography

PURPOSE To determine the agreement between peripapillary retinal nerve fiber layer (RNFL) thickness measurements from Stratus time domain optical coherence tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss Meditec, Dublin, CA) in normal subjects and subjects with glaucoma. DESIGN Evaluation of diagnostic test or technology. PARTICIPANTS A total of 130 eyes from 130 normal subjects and subjects with glaucoma were analyzed. The subjects were divided into groups by visual field criteria: normal (n = 29), glaucoma suspect (n = 12), mild glaucoma (n = 41), moderate glaucoma (n = 18), and severe glaucoma (n = 30). METHODS Peripapillary RNFL thickness was measured with Stratus Fast RNFL and Cirrus 200 x 200 Optic Disc Scan on the same day in 1 eye of each subject to determine agreement. Two operators used the same instruments for all scans. MAIN OUTCOME MEASURES Student paired t testing, Pearsons correlation coefficient, and Bland-Altman analysis of RNFL thickness measurements. RESULTS The average age of the glaucoma group was significantly more than that of the normal group: 68.3+/-12.3 years versus 55.7+/-12.1 years, respectively. For Stratus OCT, the average RNFL thickness (mean +/- standard deviation) was 99.4+/-13.2 microm, 94.5+/-15.0 microm, 79.0+/-14.5 microm, 62.7+/-10.2 microm, and 51.0+/-8.9 microm for the normal, suspect, mild, moderate, and severe groups, respectively. For Cirrus OCT, the corresponding measurements were 92.0+/-10.8 microm, 88.1+/-13.5 microm, 73.3+/-11.8 microm, 60.9+/-8.3 microm, and 55.3+/-6.6 microm. All Stratus-Cirrus differences were statistically significant by paired t testing (P<0.001) except for the moderate group (P = 0.11). For average RNFL, there was also a highly significant linear relationship between Stratus minus Cirrus difference and RNFL thickness (P<0.001). Bland-Altman plots showed that the systematic difference of Stratus measurements are smaller than Cirrus at thinner RNFL values but larger at thicker RNFL values. CONCLUSIONS RNFL thickness measurements between Stratus OCT and Cirrus OCT cannot be directly compared. Clinicians should be aware that measurements are generally higher with Stratus than with Cirrus except when the RNFL is very thin, as in severe glaucoma. This difference must be taken into account if comparing Stratus measurements with Cirrus measurements.

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.

Ability of Cirrus™ HD-OCT Optic Nerve Head Parameters to Discriminate Normal from Glaucomatous Eyes

PURPOSE To determine the ability of optic nerve head (ONH) parameters measured with spectral domain Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA) to discriminate between normal and glaucomatous eyes and to compare them with the discriminating ability of peripapillary retinal nerve fiber layer (RNFL) thickness measurements performed with Cirrus HD-OCT. DESIGN Evaluation of diagnostic test or technology. PARTICIPANTS Seventy-three subjects with glaucoma and 146 age-matched normal subjects. METHODS Peripapillary ONH parameters and RNFL thickness were measured in 1 randomly selected eye of each participant within a 200 × 200 pixel A-scan acquired with Cirrus HD-OCT centered on the ONH. MAIN OUTCOME MEASURES Optic nerve head topographic parameters, peripapillary RNFL thickness, and area under receiver operating characteristic curves (AUCs). RESULTS To distinguish normal from glaucomatous eyes, regardless of disease stage, the 6 best parameters (expressed as AUC) were vertical rim thickness (VRT, 0.963), rim area (0.962), RNFL thickness at clock-hour 7 (0.957), RNFL thickness of the inferior quadrant (0.953), vertical cup-to-disc ratio (VCDR, 0.951), and average RNFL thickness (0.950). The AUC for distinguishing between normal eyes and eyes with mild glaucoma was greatest for RNFL thickness of clock-hour 7 (0.918), VRT (0.914), rim area (0.912), RNFL thickness of inferior quadrant (0.895), average RNFL thickness (0.893), and VCDR (0.890). There were no statistically significant differences between AUCs for the best ONH parameters and RNFL thickness measurements (P > 0.05). CONCLUSIONS Cirrus HD-OCT ONH parameters are able to discriminate between normal eyes and eyes with glaucoma or even mild glaucoma. There is no difference in the ability of ONH parameters and RNFL thickness measurement, as measured with Cirrus OCT, to distinguish between normal and glaucomatous eyes.

Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes.

PURPOSE To assess the reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters measured with Cirrus HD-OCT in glaucomatous eyes. METHODS Fifty-five glaucomatous eyes were included in the study. The optic disc cube 200 × 200 protocol was used to obtain three scans during the same visit to evaluate the intravisit reproducibility. One scan on 4 additional days within a 2-month period of the first session was obtained to assess intervisit reproducibility. Intraclass correlation coefficient (ICC), coefficient of variation (CV), and test-retest SD (TRT SD) were calculated for each RNFL and ONH parameter. The formula 1.645 × √2 × intervisit TRT SD provides an upper tolerance limit to variability beyond which nonphysiologic change should be considered. RESULTS All ICCs were excellent, ranging from 83.9% to 99.2% for intravisit measurements and from 80.8% to 99.1% for intervisit measurements. Cup/disc area ratio had the lowest CV (1.1%) in either type of measurement, followed by average RNFL thickness (1.9% and 2.7%). Nasal clock hours and quadrants showed the poorest reproducibility as did the clock hour directly temporally. The intervisit tolerance limit for average RNFL thickness was 3.89 μm. CONCLUSIONS Intravisit and intervisit measurements of peripapillary RNFL thickness and ONH parameters with Cirrus HD-OCT showed excellent reproducibility, indicating that this instrument may be useful in monitoring glaucoma progression. When comparing two measurements from the same eye on two different visits, a reproducible decrease in average RNFL thickness of approximately 4 μm or more may be considered a statistically significant change from baseline.

Trabeculectomy with intraoperative mitomycin C versus 5-Fluorouracil: Prospective randomized clinical trial

OBJECTIVE To evaluate the relative efficacy and safety of 5-fluorouracil (5-FU) and mitomycin C (MMC) when used as adjuncts with primary trabeculectomy in eyes not at high risk for failure. DESIGN Prospective multicenter, randomized clinical trial. PARTICIPANTS One hundred thirteen patients with primary open-angle, pseudoexfoliative, pigmentary, or angle-closure glaucoma undergoing primary trabeculectomy were recruited. METHODS One eye of each patient was randomized to receive either 5-FU (50 mg/ml for 5 minutes) or MMC (0.4 mg/ml for 2 minutes). MAIN OUTCOME MEASURES Intraocular pressure (IOP), visual acuity, complications, and interventions were documented at fixed intervals after surgery. The study also examined progression of visual field loss, long-term complications, and bleb appearance 3 years after surgery. RESULTS Of the 108 patients with complete perioperative information, 54 eyes received 5-FU and 54 received MMC. The proportion of patients reaching different predefined target IOPs after surgery was slightly higher in the MMC group than in the 5-FU group. This difference was less than 25%, which would have been necessary to achieve statistical significance with a power of 0.8 and the sample size used. Likewise, there was no statistically significant difference between the groups with regard to mean preoperative IOP, complications, or interventions. Mean postoperative follow-up was 309 and 330 days in the 5-FU and MMC groups, respectively (P = 0.593). CONCLUSIONS 5-Fluorouracil and MMC were found to be equally safe and effective adjuncts to primary trabeculectomy in the short- and medium-term postoperative periods.