Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Pupillary light response after cataract surgery in healthy patients.

PURPOSE: To examine the changes in the pupillary light response after phacoemulsification and to compare the difference in the response among patients in different age categories. STUDY DESIGN: Prospective observational study. METHODS: Four-hundred twenty-two eyes of 422 patients in 3 age categories (60-69 years, 70-79 years, and 80-89 years) scheduled for phacoemulsification were consecutively enrolled. The eyes underwent examinations with an infrared pupillometer to obtain the parameters of the pupillary light response preoperatively and at 1 day and 1 and 3 months postoperatively. Differences in the parameters of the pupillary response were compared among 4 time intervals and the 3 age categories. RESULTS: The mean maximum and minimum pupillary diameters significantly decreased at 1 day postoperatively and returned to the preoperative level by 1 month postoperatively (P<.0001). The mean percentage of pupillary constriction was significantly reduced at 1 and 3 months postoperatively compared with preoperatively and at 1 day postoperatively (P<.0001). The average pupillary constriction and dilation velocities were significantly lower at 1 and 3 months postoperatively than they were preoperatively and at 1 day postoperatively (P<.0001). The latency to constriction did not differ significantly among the time intervals. The percentage of pupillary constriction was significantly smaller, and the average constriction and dilation velocities were lower in association with higher age categories at all time intervals (P≤.0185). CONCLUSION: The pupillary light response was impaired several months after cataract surgery and worsened with increasing patient age, indicating that cataract surgery may compromise the pupillary constriction and dilation functions in association with age.

Twelve-year follow-up of penetrating keratoplasty.

PURPOSE: To evaluate the long-term outcomes of penetrating keratoplasty (PKP) according to the corneal disease diagnosis and the number of PKP procedures performed. METHODS: Five-hundred-and-nine eyes from 403 patients who underwent PKP at Miyata Eye Hospital in Japan from 1998 through 2014, were included in this study. Medical charts were retrospectively examined to ascertain the corneal disease diagnosis and the period of graft survival. Graft survival rates were compared among various corneal disease diagnoses and among the number of PKP procedures performed. Changes in corneal endothelial cell density (ECD) were analyzed using a mixed-effects model. The presence/absence of various risk factors was compared between transparent grafts and failed grafts. RESULTS: The overall rate of graft survival at 12 years was 60.4%. The rates of graft survival in keratoconus was 100%, in corneal dystrophy 100%, in leukoma 70.8%, and in bullous keratopathy 51.7%. The rates of graft survival at 12 years for the first PKP was 65.4% and for the second PKP, 43.4% (p < 0.001). All cases of third PKP and fourth PKP failed within 8 years. Preoperative mean ECD (95% confidence interval) was 2722 (2666-2778) cells/mm2; it decreased exponentially after PKP. Mean ECD was 659 (440-878) cells/mm2 at 10 years. Rejection, trauma, and infection occurred significantly more frequently in failed grafts than in transparent grafts. CONCLUSIONS: The long-term prognosis of PKP depends on the original diagnosis. The long-term prognosis of re-grafting is worse than that of primary grafts. Rejection, trauma, and infection are risk factors for graft failure.

Comparison of Long-Term Outcomes of Visual Function and Endothelial Cell Survival After Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty Using Mixed-Effects Models.

PURPOSE: To compare the long-term outcomes of visual function and endothelial cell survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). METHODS: The cohort included 108 eyes from 97 patients who underwent primary PK and 85 eyes from 78 patients who underwent primary DSAEK at Miyata Eye Hospital in Japan. Uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), endothelial cell density, and four components from Fourier harmonic analysis of topography data (spherical component, regular astigmatism component, asymmetry component, and higher-order irregularity component) were retrospectively compared between PK and DSAEK at each time point for 5 years using mixed-effects models. Subgroup analyses were performed to compare the effect of PK and DSAEK on visual acuity. RESULTS: Average BSCVA was significantly better in the DSAEK group compared with that in the PK group both preoperatively and postoperatively. Subgroup analyses revealed that average changes in BSCVA from preoperative baseline in eyes with preoperative logarithm of the minimum angle of resolution BSCVA between 0.39 and 1.0 and between 1.3 and 2.0 were not significantly different between the PK and DSAEK groups at all postoperative time points. All components from Fourier harmonic analysis were significantly higher after PK than DSAEK at almost all postoperative time points. There were no significant differences in endothelial cell density between PK and DSAEK after 3 years. CONCLUSIONS: PK and DSAEK provide similar recovery of BSCVA and endothelial cell survival at 5 years after surgery.