Tairo Kimura

Effects of switching to SofZia-preserved travoprost in patients who presented with superficial punctate keratopathy while under treatment with latanoprost

PurposeTo investigate the effects of switching to SofZia-preserved travoprost (TRV) on superficial punctate keratopathy (SPK) observed in patients using benzalkonium chloride (BAC)-preserved latanoprost (LAT).MethodsPatients with either primary open-angle glaucoma or ocular hypertension treated with LAT for at least 1 month who presented with SPK participated in this prospective, multicenter, open-label uncontrolled study. After the switch from LAT to TRV, patients were monitored at 2 weeks and at 1, 2, and 3 months. The use of concomitantly employed ophthalmic solutions was continued during the observation period. The intensity of SPK in each of five areas defined on the cornea was scored on a standard scale. Repeated measurements were tested with a linear mixed model.ResultsOf the 48 patients enrolled, 45 patients completed the study. After the switch to TRV, the mean SPK score in the whole cornea decreased significantly at every observation point (P < 0.0001 at each point) while intraocular pressure did not change significantly. Throughout the observation period, the SPK score tended to be higher in patients using a larger number of concomitant medications that contained BAC.ConclusionSwitching to TRV improved SPK observed in a population using LAT, likely because of a decrease in exposure to BAC.

Novel Mutations in the Myocilin Gene in Japanese Glaucoma Patients

Myocilin is a gene responsible for juvenile onset primary open angle glaucoma (POAG) mapped as the GLC1A locus and, many mutations have been reported worldwide. Some mutations were found not only in patients with juvenile onset POAG, but also in patients with late onset POAG and in patients with normal tension glaucoma. To investigate the mutation prevalence in Japan, we performed a mutation analysis in 140 unrelated Japanese patients. We have identified the 10 sequence variants, of which four were highly probable for disease‐causing mutations (Arg46ter, Arg158Gln, Ile360Asn, and Ala363Thr), and six polymorphisms (Gln19His, Arg76Lys, Asp208Glu, Val439Val, Arg470His, and Ala488Ala). Thus, myocilin mutations were found at the rate of 4/140 (2.9%) probands, similar to previous reports with other ethnic populations. Hum Mutat 16:270, 2000.

Multiplex polymerase chain reaction for detection of herpes simplex virus type 1, type 2, cytomegalovirus, and Varicella-Zoster virus in ocular viral infections

PURPOSE To detect simultaneously herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), cytomegalovirus (CMV), and varicella-zoster virus (VZV) in ocular specimens suspected of indicating viral infection, and to compare the results of multiplex polymerase chain reaction (PCR) with those of uniplex PCR. METHODS Forty specimens, collected from 33 patients with clinically suspected herpes virus ocular infection, were tested. DNA was extracted from the specimens and amplified by multiplex and uniplex PCR. RESULTS Both multiplex PCR and uniplex PCR gave the same results. Nineteen (19/33, 57.6%) patients were PCR-positive, among whom HSV-1 was detected in 13 (13/19, 68.4%) patients, and VZV in 6 (6/19, 31.6%) patients. CONCLUSION These results demonstrated that multiplex PCR is as reliable as uniplex PCR, and is an accurate and a cost-saving method to identify several agents from a single specimen.

Varicella-Zoster Viral Antigen Identified in Iridocyclitis Patient

BACKGROUND The varicella-zoster virus (VZV) antigen has not been identified immunohistologically in iridocyclitis due to VZV. CASE A 65-year-old woman diagnosed with iridocyclitis and secondary glaucoma underwent trabeculectomy. Samples of aqueous humor and juxtacanalicular and iris tissue were obtained for immunohistological and polymerase chain reaction (PCR) study. OBSERVATIONS Slit-lamp microscopy revealed ciliary injection, corneal epithelial edema, mutton fat precipitates, flare, cells, and progressive iris atrophy in the right eye. Subsequently, scant eruptions on her right upper eyelid appeared and disappeared within a week. Although a diagnostic increase in the complement fixation antibody titer to VZV was not observed, we started medical treatment for VZV, on suspicion of iridocyclitis due to VZV. Despite medical treatment, the ratio of peripheral anterior synechia was greater than 60% and iris atrophy progressed in parallel. The intraocular pressure in the right eye remained above 30 mm Hg at 6 months after the first visit, so trabeculectomy was performed. VZV-specific DNA was detected in the aqueous humor by the PCR study. Immunohistological examination demonstrated numerous VZV antigen-positive cells in the iris stroma, in particular, vascular endothelial cells. CONCLUSION To our knowledge, this is the first report of the detection of VZV antigen in the iris of an iridocyclitis patient.

Acute retinal necrosis syndrome associated with herpes simplex keratitis.

Background: Although acute retinal necrosis (ARN) syndrome is caused by a herpes group virus, association of herpetic keratitis with ARN syndrome is uncommon. A case of unilateral ARN syndrome with herpes simplex keratitis is discussed. Methods: A 40-year-old man developed unilateral keratitis, necrotic retinitis, retinal vasculitis, vitritis, and iritis consistent with ARN syndrome 1 month after treatment for ipsilateral facial nerve palsy and auricular herpetic vesicles (Tolosa-Hunt syndrome). Impression cytologic examination of the corneal epithelial ulcer that developed concurrent with the intraocular findings and of the aqueous humor (obtained by paracentesis) was performed. Results: Cells that reacted with anti-herpes simplex virus type 1 (HSV-1) antibody were detected on impression cytology, and DNA fragments corresponding to the HSV-1 DNA sequence were detected in the aqueous humor. Conclusion: This case shows that ARN syndrome may, on rare occasions, be associated with herpes keratitis secondary to HSV-1.

Effect of long-term treatment with eyedrops for glaucoma on conjunctival bacterial flora.

Objective: The effect of eyedrops for glaucoma on conjunctival bacterial flora was investigated by comparing a group of patients treated with such eyedrops for at least 1 year to a control group that did not use eyedrops. Methods: In both groups, bacterial culture came from scrapings of the conjunctival sac, and the bacterial infection rate and pattern of drug resistance were determined. Findings were analyzed in various subgroups stratified by age, frequency of instillation, and concentration of antiseptic benzalkonium chloride in the eyedrops. Results: The culture-positive rate was significantly lower in the glaucoma eyedrop group (43/119 eyes, 40.3%) than in the control group (19/28 eyes, 67.8%) (P < 0.05). No differences in infection rate were found among the different age groups. The most frequent bacteria in both groups was coagulase-negative staphylococci. Gram-negative bacteria were only detected in the glaucoma eyedrop group. Retrospective evaluation was possible for 86 eyes of patients from the glaucoma eyedrop group, among which 45 eyes (52.3%) showed some corneal epithelium damage. There was no difference in the culture-positive rate of bacteria between patients who used eyedrops containing 0.01% or higher dose of benzalkonium chloride and those containing less than 0.01%. Strains that showed resistance to levofloxacin were significantly less frequent in the glaucoma eyedrop group (six strains, 15.0%) than in the control group (11 strains, 39.3%) (P < 0.05). Conclusion: Patients using eyedrops for glaucoma had a lower culture-positive rate of bacteria in the conjunctival sac, probably due to being washed out by the eyedrops. However, Gram-negative bacteria were detected in the eyedrop group. Bacteria isolated from the eyedrop group had lower resistance to levofloxacin, a finding that may have clinical relevance.

The efficacy and safety of add-on 0.1% brimonidine tartrate preserved with sodium chlorite in on-treatment Japanese normal-tension glaucoma patients

Background To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine) as add-on therapy in on-treatment Japanese normal-tension glaucoma (NTG) patients. Methods Brimonidine was added to on-treatment NTG patients with intraocular pressures (IOP) of between 13 mmHg and 16 mmHg after three consecutive IOP measurements. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 4, 8, and 12 weeks after brimonidine instillation. Results Though 75 of 83 patients (31 males and 52 females; mean age: 63.4±11.6 years) completed the study, six patients discontinued because of side effects and two patients withdrew. The mean IOP after brimonidine addition at week 4 (12.6±1.8 mmHg, P<0.001), week 8 (12.4±1.7 mmHg, P<0.001), and week 12 (12.6±1.8 mmHg, P<0.001) was significantly decreased compared with that before the addition of brimonidine (13.9±1.2 mmHg). No significant changes in superficial punctate keratitis or conjunctival hyperemia scores were observed throughout the study. Dizziness, sleepiness, eye pain, and itching (mild to moderate) were noted in five, four, three, and three patients, respectively. Conclusions The addition of newly formulated brimonidine to on-treatment Japanese NTG patients with IOP of 13–16 mmHg further reduced the levels of IOP with minimal side effects and adverse events.

Relationship between visual field progression and baseline refraction in primary open-angle glaucoma

Purpose To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma. Patients and methods In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction. Results A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (−1.9±3.8 diopter [D] vs −3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > −1D), mild myopia (−1D ≥ SE > −3D), moderate myopia (−3D ≥ SE > −6D), and severe myopia (−6D ≥ SE), the Cochran–Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03–1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94–0.99) had a significant association with MD slope deterioration. Conclusion In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.

Assessment of retinal sensitivity using a time-saving strategy in normal individuals

Background The purpose of this study was to compare retinal sensitivities in normal individuals obtained using the Swedish Interactive Threshold Algorithm Standard (SITA-S) on the Humphrey field analyzer with those obtained using the Dynamic strategy on the Octopus. Methods Prior to visual field examinations, the background luminance, stimulus size, and exposure time with the Octopus 101 were conformed to the Humphrey field analyzer II settings. Volunteers over 20 years of age without apparent ophthalmic abnormalities were examined with the SITA-S central 30-2 program followed by the Dynamic 32 program. Eye with corrected visual acuity ≥ 0.8, refraction ≥ −6.0 diopters, and fields with satisfactory levels of reliability in SITA-S and Dynamic were selected. Results Sixty-seven eyes from 67 normal individuals of mean age 51.3 ± 16.3 (range 22–76) years satisfied the selection criteria and were analyzed. Mean retinal sensitivity was significantly (P < 0.0001) higher with SITA-S (29.0 ± 2.4 dB) than with Dynamic (26.8 ± 2.1 dB). Changes in retinal sensitivity with increasing age were significantly (P = 0.0003) greater with Dynamic (−0.09 ± 0.04 dB/year; 95% confidence interval [CI] −0.10 to −0.08 dB/year) than with SITA-S (−0.07 ± 0.04 dB/year, 95% CI −0.08 to −0.06 dB/year). When classifying the visual field into three areas (central, mid-peripheral, and peripheral), retinal sensitivities with SITA-S were significantly higher in all areas than with Dynamic (P < 0.0001 for all three areas). Conclusion Differences in Dynamic and SITA-S strategies may contribute to the differences in retinal sensitivities observed in normal individuals.

Addition of or Switch to Topical Bunazosin Hydrochloride in Elderly Patients with Normal-Tension Glaucoma : A One-Year Follow-up Study

PurposeTo evaluate the efficacy and safety of 0.01% bunazosin hydrochloride ophthalmic solution (bunazosin) for elderly patients with normal-tension glaucoma (NTG) as an addition to or instead of their previous therapy.MethodsBunazosin was administered to NTG patients aged 65 years or over who had been undergoing topical glaucoma therapy. In accordance with the study protocol, intraocular pressure (IOP) and visual field measurement were performed and the safety of the treatment was evaluated periodically between week 0 and week 52 at the five facilities where the study was carried out.ResultsOf the 98 enrolled patients, 84 (85.7%) were followed up for 52 weeks. During the follow-up period, IOP significantly and persistently decreased (week 0, 15.0 ± 2.5 mmHg; week 52, 13.4 ± 2.4 mmHg, P < 0.0001), but the decrease in mean deviation (MD) was not significant. Although no systemic adverse reactions were observed, local adverse events were noted in 7 of the 98 patients.ConclusionsThe addition of or the switch to bunazosin in elderly NTG patients resulted in a significant reduction of IOP without apparent exacerbation of visual field defects or systemic or local adverse reactions other than conjunctival hyperemia. Jpn J Ophthalmol 2006;50:443–448