A nationwide survey of factors influencing adherence to ocular hypotensive eyedrops in Japan.

INTRODUCTION: Few reports have investigated the status of adherence in Japan on a large scale. We aimed to investigate the status of adherence to topical glaucoma treatment and its associated factors. METHODS: A nationwide survey was conducted as a prospective fashion. Participants in this survey were subjects with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic eyedrops and whose ophthalmologist considered prescribing any fixed combination of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects and their attending ophthalmologists independently completed a questionnaire by utilizing a fixed combination of ocular hypotensive eyedrops. RESULTS: A total of 1358 ophthalmologists from 1071 medical institutions participated in this survey. We registered 4430 subjects (2049 males and 2381 females). In total, data from 3853 subjects (87.6%) were analyzed after inclusion of subjects based on inclusion and exclusion criteria. Good adherence was defined as not forgetting instillation during the past week. Rates of good adherence reported by subjects and ophthalmologists were 72.4 and 78.5%, respectively (P < 0.0001). The consistency of adherence evaluation between subjects and ophthalmologists was moderate [kappa score 0.5025 (95% confidence interval 0.4740-0.5309)]. Significant factors associated with adherence were size of clinic, age, gender, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge of glaucoma. CONCLUSION: Adherence to ocular hypotensive eyedrops among Japanese subjects was relatively good. Concordance of adherence between subjects' reports and ophthalmologists' responses was moderate. Size of clinic, number of types of ocular hypotensive eyedrops, ease of instillation, preferred number of eyedrops, preferred frequency of instillation of eyedrops, and knowledge of glaucoma were associated with adherence among Japanese glaucoma subjects.

Cluster Formation for Analyses of Glaucomatous Visual Field Defects in Central 10-2 Visual Field in Normal Tension Glaucoma Eyes.

Purpose: To develop a cluster system to analyze the retinal sensitivity loss of 68 test points in the central 10 degrees of standard automated perimetry (SAP) in eyes with normal tension glaucoma (NTG). Patients and Methods: Patients with NTG who met the following criteria were included: visual acuity ≥0.7, SAP-derived mean deviation ≥-15 dB, and pattern deviation probability plots with at least one point with a probability of <0.5% and/or two or more contiguous points with a probability of <1% that did not cross the horizontal meridian in the central 12 points of the 24-2 test points. SAP with the Swedish Interactive Threshold Algorithm Standard (SITA-S) 10-2 program (10-2) was performed within 6 months of the SITA-S 24-2. The averaged total deviation (TD) for each of the 68 test points in the 10-2 was calculated. Hierarchical cluster analyses were performed based on the deviation of the TDs of the test points, and a dendrogram was created. The number of clusters was determined following the Sturges' rule. Results: One hundred and twenty-six eyes of 126 patients (61.9±11.4 years) were studied. Hierarchical cluster analysis of the TD values statistically obtained a dendrogram that divided the 68 test points into 7 clusters. Of these 7 clusters, 21 points belonging to the clusters in the papillomacular region included cluster 5. Cluster 5 was distributed above and below the horizontal meridian, which does not agree with the course of the retinal nerve fiber layer (RNFL). Conclusion: The hierarchical cluster analysis of the TD values stratified the 68 test points of the 10-2 into seven clusters. Considering the course of the RNFL, cluster 5 was divided into clusters of 5a and 5b, and consequently eight clusters were considered to be appropriate for detecting glaucomatous visual field defects in the central 10 degrees in NTG eyes.

Angiographic lesion size associated with LOC387715 A69S genotype in subfoveal polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy. METHODS: Ninety-two subjects with symptomatic subfoveal polypoidal choroidal vasculopathy, whose visual acuity was from 0.1 to 0.5 on the Landolt chart, were genotyped for the LOC387715 polymorphism (rs10490924) using denaturing high-performance chromatography. The angiographic phenotype, including lesion composition and size, was evaluated by evaluators who were masked for the genotype. Lesion size was assessed by the greatest linear dimension based on fluorescein or indocyanine green angiography. RESULTS: Although there was no statistically significant difference in lesion size on indocyanine green angiography (P = 0.36, Kruskal-Wallis test) and in lesion composition (P = 0.59, chi-square test) among the 3 genotypes, there was a statistically significant difference in lesion size on fluorescein angiography (P = 0.0022, Kruskal-Wallis test). CONCLUSION: The LOC387715 A69S genotype is not associated with lesion composition or size on indocyanine green angiography but with lesion size on fluorescein angiography in patients with subfoveal polypoidal choroidal vasculopathy. Because fluorescein angiography findings represent secondary exudative changes, including subretinal hemorrhages and retinal pigment epithelial detachment, the results in the present study likely indicate that the T allele at the LOC387715 gene is associated with the exudative activity of polypoidal lesions.

Changes in adherence and associated factors among patients on newly introduced prostaglandin analog and timolol fixed-combination therapy.

PURPOSE: We investigated patient adherence and factors related to a newly introduced prostaglandin analog and timolol fixed-combination eye drops (PGTFC). PATIENTS AND METHODS: The Glaucoma Research on Adherence to fixed-Combination Eye drops in Japan (GRACE) study group performed a nationwide prospective questionnaire survey. Participants in this study were patients with glaucoma who were scheduled to receive any type of PGTFC for the first time. The participants answered a questionnaire on the day of PGTFC introduction and again at a return visit 4-6 weeks after PGTFC introduction. The physicians in charge were asked to complete a separate questionnaire on the day of PGTFC introduction. One of two leaflets was randomly delivered to each participant before the description of the PGTFC. One leaflet explained how to correctly instill the eye drops, and the other explained the clinical meaning of intraocular pressure reduction in addition to explaining how to correctly instill the eye drops. Nonadherence was defined as forgetting to instill the eye drops one or more times during the week before the return visit. RESULTS: In total, 3,597 patients (age, 68.4±12.2 years) met the study protocol requirements. PGTFC introduction significantly reduced the number of antiglaucoma eye drops from 1.93±0.78 to 1.34±0.54 (P<0.0001) and significantly improved adherence (P<0.00001). Factors significantly associated with nonadherence at the return visit included a history of nonadherence as reported by either the patient or their physician before introduction, acceptable instillation times as reported by the patient, and burdensome eye drop instillation as reported by the patient. No significant difference was observed between the two leaflets in terms of their effects on adherence. CONCLUSION: PGTFC significantly improved adherence and some of the factors that were significantly associated with adherence. REGISTRATION NUMBER: UMIN000013696.

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy.

PURPOSE: To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. SUBJECTS AND METHODS: Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. RESULTS: Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P < 0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. CONCLUSIONS: Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events.

[Automated static perimetry in 5 eyes with multiple evanescent white dot syndrome].

PURPOSE: Multiple evanescent white dot syndrome (MEWDS) is a self-limiting disease in which reduced visual acuity and retinal changes recover without treatment. It also shows visual field defects including an enlarged blind spot of Mariotte. However the final outcome of the field change has rarely been documented. We therefore retrospectively studied the visual field change in eyes with MEWDS by reviewing the multiple results of automated static perimetry recorded in the clinical course of the disease. SUBJECTS: We reviewed the clinical course of five eyes with MEWDS using the multiple recordings of the Humphrey central 30-2 program taken during their clinical course. RESULTS: The initial findings of perimetry included an enlarged blind spot of Mariotte, depression of the central field, and paracentral scotoma. These field defects recovered within 2 weeks to 4 months. CONCLUSION: Visual field defects as well as vision and retinal changes recover without treatment in eyes with MEWDS.

Comparison between newly developed scanning peripheral anterior chamber depth analyzer and conventional methods of evaluating anterior chamber configuration.

PURPOSE: To compare the newly developed scanning peripheral anterior chamber depth analyzer (SPAC) with the Van Herick technique, the Shaffer grading system, and ultrasound biomicroscopy (UBM), in terms of accuracy of measurement of peripheral anterior chamber depth (ACD). METHODS: The subjects were well-controlled glaucoma patients who were being treated at the University of Yamanashi Hospital. Ten eyes from each of the 4 groups classified as Shaffer grades 1 to 4 were evaluated by SPAC, the Van Herick technique, and UBM. All measurements were performed independently on the temporal side in a masked fashion. SPAC evaluated ACD consecutively from the pupil center to the limbus at 0.4 mm intervals. UBM measurements were carried out at a depth of 500 mum (angle-opening distance 500) from the scleral spur. A dummy eye was used for evaluating SPAC measurement accuracy. RESULTS: The results of SPAC measurement were well correlated with those of the Van Herick technique and the Shaffer grading system. The SPAC measurement results were also significantly correlated with angle-opening distance 500. The correlation coefficients at distances of 2, 4, 4.8, and 5.6 mm from the pupil center were r=0.68, 0.69, 0.69, and 0.61, respectively, and the P values of all the correlations were less than 0.0001. Study of the dummy eye revealed that SPAC has high accuracy for measuring ACD and that the coefficient variances were less than 1.0% at all measured points. CONCLUSIONS: The results of SPAC measurement correlate well with those of the conventional methods.

Association between nocturnal blood pressure reduction and progression of visual field defect in patients with primary open-angle glaucoma or normal-tension glaucoma.

PURPOSE: To assess prospectively the relationship between nocturnal blood pressure reduction (dip) and progression of the visual field defect in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma (POAG). PATIENTS AND METHODS: The subjects studied were 38 patients with glaucoma (23 patients with NTG, 15 patients with POAG), in whom 48-h ambulatory blood pressure monitoring was conducted, who were followed for at least 4 years, and in whom reliable visual field tests were performed at least 5 times. The progression was determined by the mean deviation (MD) slope analysis system installed in the Humphrey field analyzer Statpac program. Glaucoma patients with a dip of <10% were assigned to the nondipper group, those with a dip of 10%-20% to the tipper group, and those with a dip of >20% to the extreme dipper group. The dipper group was defined as physiologic dippers, while the nondipper and the extreme dipper groups were defined as nonphysiologic dippers, to study the relationship between the disturbance of the dip and progression of the visual field defect. RESULTS: Thirteen patients showed significant progression, while 25 patients did not. There were no significant differences in the mean intraocular pressure and follow-up period between the patients with progression and those without progression. Half (7/14) of the nondippers, 20% (4/20) of the dippers, and 50% (2/4) of the extreme dippers showed progression, indicating a tendency of progression in the nondipper and the extreme dipper groups. The nonphysiologic dippers had a higher incidence of progression compared with the physiologic dippers (P = 0.05). Among the glaucoma patients in the nondipper and dipper categories only, those with progression had significantly smaller dips (P = 0.02). CONCLUSION: These results suggest that disturbance in the physiologic dip may be involved in the progression of glaucoma.

Ocular manifestations and prognosis of secondary glaucoma in patients with carotid-cavernous fistula.

PURPOSE: To study the frequency of ocular manifestations and the prognosis of secondary glaucoma in cases of carotid-cavernous fistula (CCF). METHODS: A retrospective multicenter study was conducted to investigate causes, types, ocular symptoms, complications, treatment, and prognosis in subjects with CCF. RESULTS: Among the 43 patients diagnosed with CCF between 1984 and 2000, a total of 13 patients (14 eyes) showed ocular manifestations. CCF was idiopathic in 13 eyes of 12 subjects and resulted from head trauma in 1 eye of 1 subject. Among the ocular symptoms and complications, conjunctival hyperemia was most common, occurring at a rate of 92.9% of the eyes, followed by exophthalmos at 50%, retinal hemorrhaging at 50%, retinal venous dilation at 42.9%, vascular bruits at 28.6%, injection of Schlemm's canal at 21.4%, and external ophthalmoplegia at 21.4%. Elevated intraocular pressure (IOP) occurred at a rate of 64.3%, with maximum IOP ranging from 22-55 mm Hg. At the time of the final observation, IOP control was favorable in 6 of the 9 eyes showing elevated IOP; 5 of these 9 eyes showed a closed CCF, but none required antiglaucoma treatment, with the exception of 1 eye for which trabeculectomy was performed. IOP control was unfavorable in the remaining 3 eyes, and in 1 of these eyes CCF was not closed. CONCLUSIONS: Secondary glaucoma is a frequently observed ocular manifestation of CCF, and closure of the fistula is the primary condition required for favorable IOP control.

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.

Bimatoprost ophthalmic solution 0.03% lowered intraocular pressure of normal-tension glaucoma with minimal adverse events.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of bimatoprost ophthalmic solution 0.03% (bimatoprost) in Japanese normal-tension glaucoma (NTG) patients with an intraocular pressure (IOP) of 18 mmHg or less. METHODS: Bimatoprost was instilled into the unilateral conjunctival sac of Japanese NTG patients with a baseline IOP of 18 mmHg or less. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 2, 4, 8, and 12 weeks post bimatoprost instillation. RESULTS: Thirty-two of the 38 enrolled NTG patients (mean age, 64.1 ± 12.6 years; 19 males and 19 females) completed the study, with six patients unable to complete the study (two patients discontinued because of side effects and four patients withdrew). The levels of IOP in the treated eyes were significantly reduced (P < 0.0001) from the baseline IOP levels. No significant change in IOP was observed in the fellow eyes. There were significant increases in conjunctival hyperemia. No significant superficial punctate keratitis scores were noted between the baseline and each point examined. Eyelash disorder, eyelid pigmentation, and deepening of the upper eyelid sulcus were observed in 28, six, and three eyes, respectively. CONCLUSION: Bimatoprost effectively lowered the IOP. It was well tolerated in Japanese NTG patients, with few patients having to discontinue because of adverse events.

Photodynamic therapy for polypoidal choroidal vasculopathy: baseline perimetric results and visual outcomes.

PURPOSE: To investigate whether the baseline mean deviation (MD) of Humphrey perimetry has a predictive value for visual improvement after photodynamic therapy (PDT) for polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the records of 40 eyes of 39 PCV patients (28 men, 11 women) who underwent PDT. The follow-up period ranged from 12 to 42 months. Best-corrected visual acuity (BCVA) improved more than 0.2 logarithm of the minimum angle of resolution (logMAR) units at the final examination in 22 (55%) of the 40 eyes, which were classified into the "Improved group." The other 18 eyes with improvement of

Long-term effects of latanoprost monotherapy on intraocular pressure in Japanese glaucoma patients.

PURPOSE: To assess the long-term effects of latanoprost monotherapy on intraocular pressure (IOP) reduction in Japanese patients with glaucoma. METHODS: Those enrolled were patients with glaucoma who had been treated on an outpatient basis for more than 5 years at the Glaucoma Outpatient Clinic of the University of Yamanashi Hospital, with only latanoprost ophthalmic solution as the first drug of choice. Subjects who underwent treatment with a drug other than latanoprost, laser therapy, or surgery were eliminated from the study, and IOP reduction by latanoprost, the dropout rate and causative reasons, and the types of additional therapy were assessed in a retrospective manner. RESULTS: Seventy-two patients (age: 68.3+/-13.0 y) were enrolled, including 40 men and 32 women for the checking of 72 eyes. There were 47 eyes with normal tension glaucoma (NTG) and 25 with primary open angle glaucoma (POAG). The mean duration of latanoprost monotherapy was 4.1+/-2.0 years (range: 5 mo to 7 y, median: 4.0 y). IOP reduction rates (cumulative dropout rates) relative to the mean IOP before the start of latanoprost monotherapy (17.8+/-3.4 mm Hg) were 11.5% (8.3%), 15.5% (8.3%), 13.0% (9.7%), 13.4% (13.9%), 13.5% (19.4%), and 10.6% (30.6%) at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years after the start of monotherapy, respectively. Although latanoprost demonstrated significant IOP reduction in POAG and NTG, eyes with POAG showed significant IOP reduction than those with NTG. Two eyes presented with local adverse events resulting from the discontinuation of use of latanoprost, and 4 eyes required filtering surgery. CONCLUSIONS: Latanoprost stably reduced IOP over a long term and maintained visual field in approximately 70% of eyes with glaucoma after treatment for 5 years.