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.

Benzalkonium Chloride Resistance in Staphylococcus epidermidis on the Ocular Surface of Glaucoma Patients Under Long-Term Administration of Eye Drops.

Purpose: We previously reported the presence of multidrug-resistant staphylococci on the ocular surface of glaucoma patients using prostaglandin analog drops for more than 1 year. Here, we investigated the effect of benzalkonium chloride (BAC) on these multidrug-resistant staphylococci. Methods: Staphylococcus epidermidis was isolated from the conjunctival sacs of 32 eyes of 32 patients comprised of 13 eyes treated with 0.005% latanoprost (Xalatan; Xa group) and 19 eyes treated with 0.004% travoprost (Travatan Z; Tz group). The minimum inhibitory concentrations (MICs) of prostaglandin analogs and BAC were measured. The presence of efflux pump genes was analyzed using polymerase chain reaction. Results: No difference was found in the MIC values of prostaglandin analogs. In contrast, the MIC values of BAC were significantly higher for the isolates from the Xa group than for those from the Tz group (2.02 vs. 1.02 µg/mL; P = 0.001). One proton-motive efflux gene, qacC/smr, was detected more frequently in the Xa isolates than in the Tz isolates (P < 0.001). The prevalence of methicillin resistance was correlated with the presence of qacC/smr (P = 0.010), and the MIC of BAC was significantly correlated with the detection of qacA/B and qacC/smr sequences (P = 0.03 and P < 0.001, respectively). Conclusions: The long-term use of eye drops containing BAC might select BAC-resistant S. epidermidis harboring qacC/smr. Translational Relevance: These findings suggest that the long-term use of eye drops containing BAC might be inappropriate in terms of avoiding antimicrobial resistance.

Conjunctival Bacteria Flora of Glaucoma Patients During Long-Term Administration of Prostaglandin Analog Drops.

Purpose: To investigate the effects of the long-term use of prostaglandin analogs for glaucoma treatment on the indigenous flora of the conjunctiva. Methods: Bacterial isolates were collected from the conjunctival sacs of 68 patients at Miyata Eye Hospital from February to September 2014, who had been receiving continuous monotherapy with prostaglandin analogs for glaucoma for at least 1 year. Minimum inhibitory concentrations of levofloxacin, gatifloxacin, moxifloxacin, cefmenoxime, tobramycin, chloramphenicol, and erythromycin against the isolates were measured to determine susceptibility. Results: The positive culture rate in all cases was 90.5% (57/63 eyes), and a total of 79 bacterial strains were isolated. The isolated bacteria included aerobic gram-positive cocci (8% Staphylococcus aureus and 41% Staphylococcus epidermidis), coagulase-negative staphylococci (5%), Streptococcus spp. (1%), Corynebacterium spp. (4%), gram-negative bacteria (4%), and the facultative anaerobe Propionibacterium acnes (33%). The positive culture rates for patients using 0.005% latanoprost (Xa group) and 0.004% travoprost (Tz group) were 88.9% and 92.6%, respectively, with no statistically significant difference in the composition of isolated bacteria between groups. Methicillin-resistant S. epidermidis (MRSE) was significantly more frequently isolated in the Xa group. The antimicrobial susceptibility rates of S. epidermidis were significantly lower in the Xa group for levofloxacin, gatifloxacin, moxifloxacin, and tobramycin. Conclusions: The indigenous flora may be affected by the long-term use of prostaglandin analogs. The higher incidence of MRSE in the Xa group should be considered during the long-term, continuous administration of eye drops, such as in glaucoma treatment.

Intraoperative mydriasis by intracameral injection of mydriatic eye drops: in vivo efficacy and in vitro safety studies.

BACKGROUND: This study investigated the efficacy and safety of intracameral injection of commercially available eye drops containing 0.5% tropicamide and 0.5% phenylephrine hydrochloride (Mydrin-P, Santen Pharmaceutical, Osaka, Japan). DESIGN: In vitro experiment and prospective clinical study at a private hospital. PARTICIPANTS AND SAMPLES: Mydrin-P was applied to confluent cultured human corneal endothelial cells, and the cellular morphology was examined. Clinical study subjects were 65 eyes of 65 patients that underwent phaco-emulsification and aspiration with intraocular lens implantation and received intracameral injection of Mydrin-P for poor mydriasis after preoperative topical instillation of mydriatics (intraocular mydriasis group; with five subgroups based on cause: diabetes, pseudo-exfoliation, post-surgery, uveitis, unknown). Controls, comprising 39 eyes of 39 patients, were not injected with Mydrin-P. METHODS: The ratio of pupillary diameter to corneal diameter was determined before and after injection of Mydrin-P. Corneal endothelial density was measured preoperatively and 3 months and 1 year postoperatively. MAIN OUTCOME MEASURES: Pupillary diameter and corneal endothelial density. RESULTS: Human corneal endothelial cell morphology was unaltered after Mydrin-P injection. The mean ratio of the pupillary diameter to corneal diameter increased in the intraocular mydriasis group (before: 54.2 ± 4.8%, after: 58.4 ± 6.6%; P < 0.001) and in the diabetes and unknown subgroups. The corneal endothelial cell density reduction rate 3 months and 1 year after surgery was not significantly different between the intraocular mydriasis group and controls. CONCLUSION: Intracameral injection of Mydrin-P appears to be effective and safe for dilating the pupil in cases with poor mydriasis after preoperative instillation of mydriatics.

Case of optic nerve involvement in metastasis of a gastrointestinal stromal tumor.

BACKGROUND: The gastrointestinal stromal tumor (GIST) belongs to the leiomyosarcoma or leiomyoma group, and metastasis of leiomyosarcoma to the orbit is extremely rare. The most common sign of the metastasis of leiomyosarcoma to the orbit is proptosis; the primary lesion is usually found in skin or soft tissue. CASE: A 60-year-old man, who had a history of multiple metastases of GIST, suffered sudden unilateral blindness. OBSERVATIONS: His history and computed tomographic scans suggested that the lesion was a metastasis of GIST to the cavernous sinus around the root of the optic nerve. CONCLUSION: To the best of our knowledge, this is the first case of metastasis of GIST to the orbit.

Oculocardiac reflex caused by contact lenses.

PURPOSE: To report two cases of patients who fell unconscious because of the oculocardiac reflex when attempting to wear contact lenses. CASE REPORTS: Case 1: A 15-year-old healthy boy came to our clinic to be fitted with contact lenses. As soon as a hard contact lens was inserted forcibly, he became unconscious. Case 2: A 22-year-old man fell unconscious the instant that the eye was compressed with a hard contact lens. Neither patient had used glasses or contact lenses before. Their blood pressure was decreased while unconscious. They recovered consciousness after about 10 min, and nausea and vomiting settled subsequently. Contact lens insertion was tried again carefully after 1 week avoiding compression of the eyes and there were no problems. They are currently using contact lenses without any problems. CONCLUSION: Insertion of contact lenses may rarely provoke the oculocardiac reflex.

Inhibition of murine corneal allograft rejection by treatment with antibodies to CD80 and CD86.

The purpose of this study was to investigate the role of CD80 and CD86 costimulatory molecules in corneal allograft rejection. Anti-CD80 and anti-CD86 monoclonal antibodies (mAbs) were administered after orthotopic corneal allograft transplantation. Graft rejection was observed by biomicroscopy. Population and localization of CD80(+)and CD86(+)cells in the cornea, cervical lymph nodes, and spleen were examined by flow cytometry and immunohistochemistry. The combined use of anti-CD80 and anti-CD86 mAbs was effective in prolonging corneal allograft survival. In the untreated mice bearing rejected graft, many CD86(+)and CD80(+)cells were found around the host-graft junctional area in the cornea, and CD86(high)cells were found in the cervical lymph node and spleen. In contrast, few CD86(+)or CD80(+)cells were observed in the cornea, cervical lymph node, and spleen from the mice treated with anti-CD80/CD86 mAbs. These results demonstrated a significant role of CD80 and CD86 costimulatory molecules in corneal allograft rejection.

Fourier series harmonic analysis of corneal topography following suture removal after penetrating keratoplasty.

PURPOSE: To evaluate quantitatively the influence of suture removal after penetrating keratoplasty on corneal refraction including irregular astigmatism. METHODS: Subjects were 42 eyes of 39 patients with clear corneal grafts who underwent suture removal after penetrating keratoplasty. Videokeratography data taken before and after suture removal were decomposed using Fourier harmonic analysis into spherical power, regular astigmatism, and irregular astigmatism (asymmetry and higher order irregularity). RESULTS: On average, spherical power significantly increased after suture removal (p < 0.0001, paired t test), and regular astigmatism did not change significantly (p = 0.247). Suture removal significantly decreased asymmetry (p < 0.0001) and higher order irregularity (p < 0.0001). CONCLUSIONS: Suture removal after penetrating keratoplasty induces myopic shift and reduction in irregular astigmatism of the cornea.

Intraocular dexamethasone delivery system for corneal transplantation in an animal model.

PURPOSE: To assess the efficacy of a new intraocular biodegradable polymer dexamethasone drug delivery system (DEX DDS) in a high-risk corneal transplantation model. METHODS: Lewis rats that received orthotopic corneal transplants (Balb/c mice donors) were divided into three groups (six rats in each); group 1 received no treatment and served as controls, group 2 was treated with 0.1% betamethasone eyedrops three times daily for 6 weeks, and group 3 received DEX DDS in the anterior chamber at the time of transplantation. RESULTS: All grafts in the untreated control group were rejected within 8 days. In the betamethasone eyedrop group, five eyes (83%) were rejected during the 8-week study period. None of the grafts in the DEX DDS group was rejected. The administration of DEX DDS significantly prolonged the survival rate of the corneal grafts (p < 0.001, log-rank test). CONCLUSION: DEX DDS is effective in suppressing graft rejection in high-risk corneal transplantation.