Katsuhiko Maruyama

Additive effect of dorzolamide or carteolol to latanoprost in primary open-angle glaucoma: a prospective randomized crossover trial.

PurposeTo compare the additive effect of dorzolamide or carteolol to latanoprost on intraocular pressure (IOP) in glaucoma patients. DesignProspective open-label randomized crossover clinical study. MethodsA total of 64 patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months then randomized to receive latanoprost plus dorzolamide 1% 3 times daily (dorzolamide preceding group; n=32) or carteolol hydrochloride 2% twice daily (carteolol preceding group; n=32) for a further 3 months. Then, all patients were crossed over to the opposite treatment arm for a further 3 months. IOP was recorded each month at around the time same as on the baseline day. ResultsSixty-one patients (95%) completed this trial. In the dorzolamide preceding group, mean (±SD) IOP was 19.0±2.1 mm Hg at baseline and 16.0±2.1 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of dorzolamide reduced IOP to 15.0±1.3 mm Hg and this was not changed by switching to carteolol (15.1±1.7 mm Hg). In the carteolol preceding group, IOP was 19.1±1.9 mm Hg at baseline and 16.2±1.2 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of carteolol reduced IOP to 14.9±1.5 mm Hg, and after switching to dorzolamide IOP was 15.2±1.5 mm Hg. Mean additional IOP reduction was 0.9±1.2 mm Hg (5.6%) for the latanoprost-dorzolamide combination and 1.1±1.5 mmHg (6.8%) for the latanoprost-carteolol combination. Hence, IOP reduction by carteolol and dorzolamide additionally to latanoprost was not different. ConclusionsBoth dorzolamide and carteolol reduce IOP additively when used in combination with latanoprost, and the additive effect of these drugs is equal.

Incidence of deepening of the upper eyelid sulcus after topical use of travoprost ophthalmic solution in Japanese.

Purpose:To investigate the incidence of deepening of the upper eyelid sulcus (DUES) with topical use of travoprost in Japanese glaucoma patients. Patients and Methods:This prospective study enrolled 32 primary open-angle glaucoma Japanese patients who had been treated topically with travoprost unilaterally for 6 months at baseline, and started treatment in both eyes. The patients were observed during outpatient visits at 2, 4, and 6 months. At every visit, the photographs of both eyes and forehead were displayed randomly and the presence of DUES was diagnosed when 3 examiners unanimously rated the case as positive. The patients were also asked if they noticed any subjective symptom of DUES. Sex, refraction, and intraocular pressure (IOP) were evaluated as potential risk factors. Results:DUES was identified objectively in 34% (11/32) of the patients after 2 months of treatment, and in 53% (17/32) after 4 and 6 months of treatment. The incidence was significantly higher in older patients (P<0.05), but not related to sex, refraction, pretreatment and posttreatment IOP, and IOP reduction. Finally, 41% (7/17) of patients with objectively diagnosed DUES noticed the presence of DUES by themselves. No patient dropped out of the study because of DUES. Conclusions:DUES is a common side effect of topical travoprost treatment in Japanese glaucoma patients.

Comparison of the Additive Effects of Nipradilol and Carteolol to Latanoprost in Open-Angle Glaucoma

PurposeTo compare the effects of nipradilol and carteolol on intraocular pressure (IOP) when added to latanoprost treatment for glaucoma patients.MethodsFifty patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months. Then they were assigned to one of two groups randomly. One group received nipradilol 0.25% twice daily (nipradilol preceding group; n = 25), and the other carteolol hydrochloride 2% twice daily (carteolol preceding group; n = 25), for 3 months in addition to latanoprost. Then, nipradilol and carteolol were switched, and the subjects were treated for 3 more months. One eye was selected randomly for analysis.ResultsIn the nipradilol preceding group, IOP was 21.4 ± 2.3 mmHg (mean ± SD) at baseline, and 16.8 ± 1.9 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of nipradilol decreased IOP to 15.8 ± 1.7 mmHg, and the change to carteolol, to 15.3 ± 2.0 mmHg. In the carteolol preceding group, IOP was 21.2 ± 2.0 mmHg at baseline, and 17.0 ± 2.1 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of carteolol decreased IOP to 15.4 ± 1.8 mmHg, and the change to nipradilol, to 16.3 ± 1.9 mmHg. Additional IOP reduction was greater with carteolol than with nipradilol (cross-over analysis of variance; P = 0.0005).ConclusionsBoth nipradilol and carteolol have additive effects when used in combination with latanoprost. Carteolol, however, may have a more potent effect than nipradilol. Jpn J Ophthalmol 2006;50:33–37

Conjunctival Flora in Patients with Human Immunodeficiency Virus Infection

Purpose: To compare the conjunctival flora of human immunodeficiency virus (HIV)-positive and HIV-negative patients. Also, to assess the prophylactic effect of oral clarithromycin against Mycobacterium avium complex on the conjunctival flora of HIV-positive patients. Methods: Ninety-four eyes of 47 HIV-positive patients and 122 eyes of 61 control patients were examined. All participants had a detailed anterior segment examination, including conjunctival cultures and laboratory blood tests. Culture results for different organisms were evaluated by chi-square analysis between the groups. The effect of systemic antibiotic treatment on the conjunctival flora of patients with HIV infection was evaluated by chi-square analysis. Results: Bacterial organisms in the conjunctival sac were detected in four out of 28 (14.3%) eyes of HIV-positive patients treated with systemic clarithromycin and in 32 out of 66 (48.5%) eyes of HIV-positive patients without systemic clarithromycin treatment (p < 0.01). The CD4-positive T-cell counts in these groups were 158/μl and 416/μl, respectively (p < 0.01). Bacterial organisms were also detected in 46 of 122 (37.7%) control eyes. No difference was observed in the types and proportions of organisms isolated from the conjunctiva between HIV-positive patients without systemic clarithromycin treatment and controls. Conclusion: There was no difference between the conjunctival flora of HIV-negative and HIV-positive patients. Systemic clarithromycin treatment decreased the conjunctival flora of HIV patients, including those who had a CD4 count that was less than 50/μl.

Incidence of Postoperative Ptosis Following Trabeculectomy With Mitomycin C

Purpose:To prospectively investigate the incidence of postoperative ptosis following trabeculectomy by comparing preoperative and postoperative margin reflex distance (MRD), and to analyze the clinical factors associated with ptosis. Patients and Methods:Patients who underwent trabeculectomy with mitomycin C in unilateral eye between 2010 and 2012 were enrolled. MRD was measured before and 3 and 6 months after trabeculectomy. The MRD is the distance between the light reflex at central cornea and the upper eyelid margin when the patient gazed at a pen light placed 50 cm away straightly. Postoperative ptosis was defined as a decrease in MRD≥2 mm from preoperative level. The correlation among &Dgr;MRD (difference between preoperative and 6 mo postoperative MRD) and clinical factors comprising age, spherical equivalent, preoperative MRD, 6-month postoperative intraocular pressure (IOP), and IOP reduction (difference between preoperative and 6 mo postoperative IOP) was analyzed. Results:Thirty-six patients (36 eyes) were analyzed. Preoperative median MRD was not different between the operated eye and nonoperated fellow eye (both 4.0 mm, P=0.65). The 3- and 6-month postoperative MRD in the operated eye were significantly reduced compared with preoperative MRD (3.0 mm, P=0.04 and 2.5 mm, P=0.01, respectively). The 3- and 6-month postoperative MRD in the nonoperated eye were not different from preoperative MRD (4.0 mm, P=0.81 and 4.0 mm, P=0.85, respectively). The incidence of ptosis at 6 months after operation was 19% (7 of 36 eyes). The IOP was significantly decreased at 3 and 6 months after operation (both P<0.01). No correlation was observed between &Dgr;MRD and all the factors analyzed. Conclusions:Ptosis is a major complication following trabeculectomy with mitomycin C, with an incidence of 19% at 6 months after operation.

Incidence of deepening of upper eyelid sulcus after topical use of tafluprost ophthalmic solution in Japanese patients

Purpose To investigate the incidence of deepening of upper eyelid sulcus (DUES) with topical use of tafluprost in Japanese glaucoma patients. Methods This study was a prospective, open-label, non-controlled case series conducted at a single center. Thirty-six primary open-angle glaucoma Japanese patients who had no history of surgery were enrolled. The patients were prescribed 0.0015% topical tafluprost once daily to one eye that had the more severe visual field disorder, and observed during outpatient visits before and at 30, 60, and 90 days after starting treatment. At every visit, three examiners judged the presence of DUES unanimously by facial photographs including eyebrows and lower eyelids. The primary outcome variable was the incidence of DUES at the end of day 90 in the study as assessed by observer-masked facial photography. The patients were also asked if they noticed any subjective symptom of DUES. Gender, refraction, and intraocular pressure were evaluated as potential risk factors. Results Thirty-two patients completed this clinical trial. DUES were identified objectively in 19% (6/32) of the patients after 90 days of treatment. The incidence was not related to gender, refraction, baseline or post-treatment intraocular pressure, or intraocular pressure reduction. Finally, 17% (1/6) of patients with objectively diagnosed DUES noticed the presence of DUES by themselves. No patient dropped out of the study because of DUES. Conclusion Similar to other prostaglandin analogs, topical use of tafluprost ophthalmic solution is associated with DUES as a local adverse reaction.

Human iris pigment epithelial cells suppress T-cell activation via direct cell contact ☆

The purposes of the present study were to investigate whether cultured human iris pigment epithelial (hIPE) cells acquire the ability to modify T-cell activation, and if so, to identify the mechanism. Human IPE cells were prepared from patients who underwent glaucoma surgery, and were cultured in RPMI 1640 medium containing 10% fetal calf serum for 4-7 days. Expression of MHC molecules and co-stimulatory molecules on cultured hIPE cells either unstimulated or stimulated with IFN-gamma was examined by FACS. In addition, peripheral blood T cells were incubated with cultured hIPE cells prepared from the same patients and anti-CD3 antibody in a transwell culture system, or in the presence of anti-PD-L1 and PD-L2 antibodies, and T cell proliferation was assessed by [3H]-thymidine incorporation. The hIPE cells inhibited anti-CD3-driven T-cell activation but the inhibition was diminished when tested in the transwell culture system, indicating that a contact-dependent mechanism is important in the immunoregulatory roles of hIPE. Although cultured hIPE cells expressed Class I and PD-L1 but not Class II or PD-L2, all these molecules were observed on hIPE cells cultured in the presence of IFN-gamma. Blocking antibodies against both PD-L1 and PD-L2 reduced the immunoregulatory activity of hIPE cells. Our data indicates that cultured hIPE cells inhibit T-cell activation by T-cell receptor ligation, which is mediated by cell-to-cell contact in part via the PD-L1 and PD-L2 pathways.