Bret A. Hughes

A three-month, multicenter, double-masked study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to travoprost 0.004% ophthalmic solution and timolol 0.5% dosed concomitantly in subjects with open angle glaucoma or ocular hypertension.

Purpose:The primary objective of this study was to compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination to the concomitant administration of travoprost 0.004% (TRAVATAN®) and timolol 0.5% in subjects with open angle glaucoma or ocular hypertension. Methods:This was a randomized, multicenter, double-masked, active-controlled, parallel group study. Three hundred sixteen patients with open angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.004%/timolol 0.5% ophthalmic solution fixed combination once daily in the morning or concomitant administration of timolol 0.5% once daily in the morning and travoprost 0.004% ophthalmic solution once daily in the evening. The efficacy and safety of the fixed combination were compared with concomitant therapy over three months. The primary efficacy outcome measure was mean intraocular pressure. Results:Both travoprost 0.004%/timolol 0.5% fixed combination and the concomitant administration of travoprost 0.004% and timolol 0.5% produced statistically significant reductions from baseline in IOP, with mean IOP ranging from 15.2 to 16.5 mm Hg in the patients using travoprost 0.004%/timolol 0.5% fixed combination compared with 14.7 to 16.1 mm Hg in the concomitant group. The upper 95.1% confidence limit for the differences in mean IOP (fixed combination minus concomitant) was ≤1.5 mm Hg at 7 of 9 visits, including all three 8 AM time points, 24-hours post-dose. Mean IOP reductions from baseline ranged from 7.4 to 9.4 mm Hg in the fixed combination group compared with 8.4 to 9.4 mm Hg with concomitant therapy. Safety analysis demonstrated equivalent safety between the two treatment groups. Conclusions:A fixed combination of travoprost 0.004% and timolol 0.5% produced clinically relevant IOP reductions in patients with open angle glaucoma or ocular hypertension that were comparable to concomitant therapy with its components. Safety and tolerability of the fixed combination were also equivalent to concomitant therapy. Travoprost 0.004%/timolol 0.5% fixed combination offers IOP reduction equivalent to concomitant therapy, with potential benefits that include convenience (fewer bottles and drops per day), improved compliance, cost savings (based on fewer co-payments), and elimination of potential washout effects.

Primary Glaucoma Triple Procedure with or without Adjunctive Mitomycin: Prognostic Factors for Filtration Failure

PURPOSE The prerequisite for selective use of adjunctive mitomycin C (MMC) in primary glaucoma triple procedure (PGTP) is a better understanding of the prognostic factors. Therefore, the authors carried out the current study on the outcome of PGTP with and without adjunctive MMC to determine the prognostic factors for filtration failure of PGTP. METHODS The study patients consisted of 174 consecutive primary open-angle glaucoma (POAG) patients undergoing PGTP. They were assigned randomly to either no adjunctive MMC (93 eyes of 93 patients) or adjunctive subconjunctival MMC (81 eyes of 81 patients) during the PGTP. After surgery, the patients were examined at regular intervals for visual acuity, intraocular pressure (IOP) control, medical therapy requirements, and complications. Filtration failure was determined according to two different criteria: (1) a less stringent set of criteria (criterion I) and (2) a more stringent set of criteria (criterion II). RESULTS There were no statistically significant differences between the groups with and without adjunctive MMC with respect to postoperative IOP, number of medications, and visual acuity outcome during mean follow-up (+/- standard deviation) of 25.1 +/- 5.5 months (P > 0.05 for each). However, there were prognostic factors for filtration failure in the control group but not in the MMC group. Black race, diabetes mellitus, preoperative IOP greater than or equal to 20 mmHg, and number of preoperative medications greater than two were found to be significant prognostic factors for filtration failure by criterion I. Black race, preoperative IOP greater than or equal to 20 mmHg and number of preoperative medications greater than 1 were significant prognostic factors for filtration failure by criterion II. CONCLUSION There was no statistically significant difference in the overall outcome of PGTP between control and MMC groups of nonselected patients with primary open-angle glaucoma. Black race, diabetes mellitus (by criterion I only), preoperative IOP greater than or equal to 20 mmHg, and number of preoperative medications greater than 2 (by criterion I) or greater than 1 (by criterion II) were found to be significant independent prognostic factors for filtration failure of PGTP without adjunctive MMC but no with adjunctive MMC. The use of adjunctive subconjunctival MMC in PGTP may have to be selective, primarily in those patients with primary open-angle glaucoma with one or more of the prognostic factors for filtration failure.

Limbus-based vs fornix-based conjunctival flap in combined glaucoma and cataract surgery with adjunctive mitomycin C

PURPOSE To determine the efficacy and safety of limbus-based vs fornix-based conjunctival flaps in patients with primary open-angle glaucoma undergoing trabeculectomy combined with phacoemulsification and intraocular lens implantation with adjunctive subconjunctival mitomycin C. METHODS In a prospective study, 69 eyes of 69 patients with primary open-angle glaucoma, visually symptomatic cataracts, and no previous incisional ocular surgery were randomly assigned to limbus-based and fornix-based conjunctival flap groups. All patients received trabeculectomy combined with phacoemulsification and posterior chamber lens implantation with 1-minute (0.5 mg/ ml) application of subconjunctival mitomycin C. RESULTS The mean intraocular pressures were significantly (P < .05) lower on significantly (P < .05) fewer medications postoperatively at 1 week, 1 month, 3, 6, 9, 12, and 15 to 18 months, and at last follow-up in both groups than they had been preoperatively. However, there were no significant (P > .05) differences in postoperative mean intraocular pressure, mean number of medications, and visual acuity between the two groups at any time interval. Hypotony with wound leak was significantly (P = .019) higher in the limbus-based group. Other postoperative complications were not significantly (P > .05) different between the two groups. CONCLUSIONS There was no notable difference in glaucoma control or visual outcome between limbus-based and fornix-based conjunctival flaps in primary trabeculectomy combined with phacoemulsification and lens implantation with adjunctive subconjunctival mitomycin C. The fornix-based flap was as safe as, if not safer than, the limbus-based flap in the glaucoma triple procedure with adjunctive subconjunctival mitomycin C.

Primary glaucoma triple procedure in patients with primary open-angle glaucoma: The effect of mitomycin C in patients with and without prognostic factors for filtration failure

PURPOSE To investigate the effect of adjunctive mitomycin C on primary glaucoma triple procedure in patients with primary open-angle glaucoma with and without one or more of the prognostic factors for filtration failure of primary glaucoma triple procedure. Those factors include being of African-American race, having a preoperative intraocular pressure of 20 mm Hg or more on maximum tolerated medications, and being on two or more medications preoperatively. METHODS Study patients consisted of 197 consecutive patients with primary open-angle glaucoma who were randomly assigned to receive either no adjunctive mitomycin C (101 eyes of 101 patients) or to receive adjunctive subconjunctival mitomycin C (96 eyes of 96 patients) during the primary glaucoma triple procedure. Kaplan-Meier survival analysis comparisons were made between respective subgroups with and without prognostic indicators for filtration failures using a relatively stringent set of criteria for filtration success of primary glaucoma triple procedure. RESULTS There was no statistically significant (P = .117) difference in filtration success of primary glaucoma triple procedure between the control and mitomycin C groups. Adjunctive mitomycin C significantly (P < .05) improved the filtration outcome of the primary glaucoma triple procedure in the subgroups with each of the three prognostic factors for filtration failure of primary glaucoma triple procedure. On the other hand, in the subgroups without the prognostic factors, adjunctive mitomycin C did not significantly (P > .05) change the filtration outcome of the primary glaucoma triple procedure. CONCLUSION These findings establish the basis for selective use of mitomycin C in patients with primary open-angle glaucoma undergoing primary glaucoma triple procedure.

Adjunctive Subconjunctival Mitomycin C in Glaucoma Triple Procedure

PURPOSE To evaluate the potential benefit of adjunctive subconjunctival mitomycin in patients with primary open-angle glaucoma undergoing primary trabeculectomy combined with phacoemulsification and intraocular lens implantation. METHODS Seventy-eight eyes of 78 patients with primary open-angle glaucoma with visually symptomatic cataracts and no previous incisional surgery were randomized to receive either no mitomycin C or a subconjunctival application of 1-, 3-, or 5-minute mitomycin C (0.5 mg/ml). RESULTS Follow-up (mean +/- standard deviation) was 21.0 +/- 7.7 months. The mean postoperative intraocular pressures were significantly lower with significantly less medications than the preoperative values at each follow-up time (1, 3, 6, 9, 12, 15 months, and last follow-up) for all groups (P < 0.05 for each). However, there was no significant difference at each follow-up time in intraocular pressure, medications, or best-corrected visual acuity among the four groups or between the control and the total mitomycin C group. CONCLUSION Adjunctive subconjunctival mitomycin C did not further improve the final intraocular pressure outcome of the primary trabeculectomy combined with phacoemulsification and intraocular lens implantation in patients with primary open-angle glaucoma. Future studies will determine the appropriate role, if any, for adjunctive mitomycin C in selected primary glaucoma triple procedures.

Comparison of the Safety and Efficacy of Dorzolamide 2% and Brimonidine 0.2% in Patients with Glaucoma or Ocular Hypertension

Purpose:To compare the intraocular pressure (IOP) reduction between dorzolamide 2% and brimonidine 0.2% in primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Methods:This study was a prospective, double-masked, randomized, crossover comparison of dorzolamide 2% (Trusopt®) and brimonidine 0.2% (Alphagan®), three times daily during two six-week study periods. The primary endpoint was mean change from baseline in trough IOP and secondary endpoints were mean change from baseline in IOP one and three hours after dosing. T-tests and a repeated-measures ANOVA were used to statistically evaluate the data. Results:Of 43 patients enrolled, 41 completed the first treatment and 38 completed both treatments. Baseline IOP for dorzolamide was 24.3 mm Hg and brimonidine, 24.6 mm Hg (P = 0.9). Mean IOP reduction at trough was similar for both agents, 3.0 mm Hg (P = 0.96). Reductions at one and three hours were comparable (P = ns). Both agents were well tolerated with adverse events consistent with the package inserts. Dorzolamide was associated with more frequent stinging (P = 0.017) and burning (P < 0.001), while brimonidine was associated with more frequent dry eye (P = 0.04). Conclusions:Dorzolamide and brimonidine, as monotherapy, produced equivalent IOP-lowering efficacy at trough and at one and three hours after instillation, and both were well tolerated.

The additive effect of latanoprost to maximum-tolerated medications with low-dose, high-dose, or no pilocarpine therapy

OBJECTIVE To assess the efficacy of latanoprost additive therapy in patients with intraocular pressure (IOP) out of control while taking maximum-tolerated medications and to determine whether pilocarpine therapy has a dose-dependent adverse effect on the efficacy of latanoprost therapy. DESIGN Noncomparative case series. PARTICIPANTS Sixty-one eyes of 61 patients with chronic glaucoma with IOP out of control while receiving maximum-tolerated medications were treated with latanoprost additive therapy on a compassionate basis. MAIN OUTCOME MEASURES Follow-up was up to 22 months with a mean of 13.9 +/- 5.7 months. Kaplan-Meier survival analysis with Mantel-Cox log-rank test was performed to determine the overall success of latanoprost additive therapy and to compare the success rates of high-dose pilocarpine, low-dose pilocarpine, and no pilocarpine therapies. The criterion for success was avoiding glaucoma surgery with IOP decrease of 20% or greater and final IOP less than 22 mmHg. The IOP change and its significance for patients satisfying and failing the criterion for success also were determined to assess the latanoprost additive therapy. In addition, a number of pretreatment variables, including pilocarpine therapy, were analyzed for a significant effect on the efficacy of latanoprost additive therapy using Cox proportional hazards regression analysis. RESULTS Latanoprost additive therapy significantly lowered mean IOP by 3.9 +/- 5.5 mmHg at 3 months and by 3.5 +/- 5.8 mmHg at 12 months. The cumulative success rate of the latanoprost additive therapy was 70% at 1 month, 42% at 3 months, 40% at 6 months, and 30% at 12 months. Of the variables studied, only increased number of previous incisional glaucoma surgeries and IOP greater than 24 mmHg before latanoprost additive therapy were significant prognostic factors for failure of latanoprost additive therapy. Pilocarpine therapy in any dose had no significant effect. CONCLUSION This study supports a trial of latanoprost additive therapy before glaucoma surgery in patients with IOP out of control while receiving maximum-tolerated medications irrespective of pilocarpine therapy and the pilocarpine dosage, especially when the number of previous incisional glaucoma surgery is less than three and the IOP is less than 25 mmHg.

Long-term filtration and visual field outcomes after primary glaucoma triple procedure with and without mitomycin-C

OBJECTIVE To evaluate the long-term effectiveness of glaucoma management in patients undergoing primary glaucoma triple procedure (PGTP) with and without adjunctive subconjunctival mitomycin-C (MMC). DESIGN Case-controlled study. PARTICIPANTS Of the 203 eyes of 203 primary open-angle glaucoma (POAG) patients who had undergone PGTP and in whom reliable Humphrey visual fields had been obtained both before and after surgery at 13.5 +/- 8.9 and 27.9 +/- 8.9 months, 124 of the 144 eyes that received MMC during surgery were matched to the other 59 eyes that did not with respect to cup-to-disc ratio and risk factors for filtration failure in addition to other variables. MAIN OUTCOME MEASURES Both preoperative and postoperative intraocular pressure (IOP), Humphrey visual fields and their global indices, number of glaucoma medications, and best-corrected visual acuity (BCVA). RESULTS There were no significant differences in demographics between the two groups (P > 0.05 for each). Whereas both the control and the MMC groups attained significant decreases of mean IOP (18.5 +/- 5.7 mmHg-;15.6 +/- 4.6 mmHg, P = 0.0014; 19.3 +/- 7.0 mmHg-13.7 +/- 4.9 mmHg, P = 0.0001) and mean number of medications (2.1 +/- 1.3-1.3 +/- 1.3, P = 0.0001; 2.3 +/- 1.2-1.0 +/- 1.3, P = 0.0001) at 36 months after surgery, the MMC group had significantly lower mean IOP than the control group at all postoperative visits (P < 0.05 for each). The MMC group also tended to have less medical dependency after surgery than the control group. There was no significant difference in postoperative BCVA between the two groups. Patients in both groups had mean visual acuity of 20/30 or better. There was a significant worsening of corrected pattern standard deviation (CPSD) in the control group (3.97 +/- 3.18-5.17 +/- 3.36, P = 0.001) compared with no significant change in the MMC group (5.07 +/- 4.11-5.23 +/- 3.36, P = 0.93). The mean deviation did not change significantly in either group. CONCLUSIONS The long-term glaucoma management in POAG patients with cataract undergoing PGTP indicates a successful outcome in final IOP, medical dependency, and BCVA. Furthermore, the MMC group had better IOP control and stable visual fields (CPSD), whereas the control group had a significant worsening of CPSD.

Long-term outcome of primary glaucoma triple procedure with adjunctive 5-fluorouracil

Abstract · Purpose: To evaluate the long-term effect of adjunctive subconjunctival 5-fluorouracil (5-FU) on the filtration outcome of primary glaucoma triple procedure (PGTP) in primary open-angle glaucoma (POAG) patients. · Methods: Seventy-four POAG patients were randomly assigned to PGTP alone (36 patients) or PGTP with adjunctive subconjunctival 5-FU (5.0 ± 1.3 injections of 5 mg each, total of 24.8 mg) (38 patients). After surgery, the patients were examined at regular intervals for intraocular pressure (IOP), visual acuity, medical therapy requirements, and complications. Surgical success was defined as IOP ≤20 mmHg on postoperative medication ≤1 without additional glaucoma surgery. · Results: Over an average follow-up (±SD) of 45.3 ± 25.0 months, both 5-FU and control groups maintained significant improvement of IOP control and visual acuity. However, there were no statistically significant differences between the 5-FU and control groups with respect to postoperative IOP, number of glaucoma medications, visual acuity outcome, and success rate overall or in selected patients with one or more of the risk factors for filtration failure. · Conclusions: The use of low-dose subconjunctival 5-FU (mean dosage of 24.8 mg in 5.0 ± 1.3 injections) as an adjunct did not significantly improve the long-term filtration outcome of PGTP in POAG patients.

Comparative Study of Silicone versus Acrylic Foldable Lens Implantation in Primary Glaucoma Triple Procedure

OBJECTIVE To compare silicone versus acrylic foldable intraocular lens (IOL) implantation in primary glaucoma triple procedure (PGTP). DESIGN Prospective, randomized. PARTICIPANTS A total of 79 eyes of 79 primary open-angle glaucoma (POAG) patients in need of combined surgery were randomized to a silicone IOL group (36 eyes) and acrylic IOL group (43 eyes). INTERVENTION The study eyes underwent PGTP, which consisted of primary trabeculectomy, phacoemulsification, and posterior chamber IOL implantation. Adjunctive mitomycin C (MMC) (0.5 mg/ml for 1 minute) was used selectively only in patients with one or more risk factors for filtration failure of PGTP. MAIN OUTCOME MEASURES Snellen visual acuity, intraocular pressure (IOP), slit-lamp biomicroscopy, and number of glaucoma medications were measured, performed, or determined preoperatively and at regular intervals postoperatively. RESULTS There were no significant differences in the mean number of postoperative glaucoma medications at 1, 2, 3, 4-6, and 9-12 months and at last follow-up (P > 0.05); mean change in corrected visual acuity best attained (P = 0.315) or at last follow-up (P = 0.223) between the silicone and acrylic groups. Both groups had significant decreases in mean IOP and mean number of medications postoperatively at all times (P < 0.05). However, the postoperative IOP > 25 mmHg and IOP spike > 5 mmHg above preoperative IOP during the first month were significantly higher in the acrylic group (P = 0.026). The mean postoperative IOP at 1 month in the acrylic group was also significantly higher than the silicone group (14.1 +/- 5.0, 11.2 +/- 3.9, P = 0.005). Conversely, there were no significant differences in mean postoperative IOP at 2, 3, 4-6, and 9-12 months and at last follow-up between the silicone and acrylic groups (P > 0.05). Suture removal or release occurred significantly more frequently in the acrylic IOL group during the first month and the first 2 months (48.8% and 60.5%) than the silicone group (25.0% and 36.1%, P = 0.030 and 0.031, respectively). There were no significant differences in postoperative complications or surgical interventions between the two groups (P > 0.05). CONCLUSIONS During the first year following the PGTP with selective use of MMC, there were no significant differences in the medical dependency or visual outcomes or complications between the silicone and acrylic groups. Both groups attained significant decreases in IOP postoperatively. However, the mean IOP was significantly higher in the acrylic than the silicone group at 1 month postoperatively, and postoperative IOP > 25 mmHg and IOP spike > 5 mmHg above preoperative IOP were significantly greater in the acrylic group. There were significantly more suture releases in the acrylic IOL group than the silicone IOL group in the first 2 months postoperatively.