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.

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.

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.

The Correlation Between Aqueous Humor Flow and IOP Before and After Trabectome: Developing a Grading System to Quantify Flow.

INTRODUCTION: To develop a grading system that provides objective quantification of flow through the conventional aqueous humor outflow (AHO) system. The technique gives clinicians an additional assessment option in the evaluation of glaucoma treatment approaches. METHODS: This was a retrospective observational study. This study evaluated the eyes of all primary open-angle glaucoma patients who underwent a Trabectome (NeoMedix Corp., Tustin, CA, USA) procedure with or without cataract surgery in the interval between April and September 2016 (n = 73). The nasal hemisphere was divided into three regions. Utilizing a four-level grading system designed for this study, an aqueous humor outflow grade (G0-G3) was assigned to each region using a video taken during examinations. The individual grade levels of the three regions were combined to get a composite AHO score. The correlation between the composite AHO score and intraocular pressure (IOP) was then analyzed. Additionally, the speed of red blood cell (RBC) clusters in the episcleral veins (ESV) was calculated when made possible by the existence of pulsatile flow. RESULTS: At 3 months following the Trabectome procedure, average IOP decreased from 26 to 15 mmHg. Assessment of the relationship between AHO grade and IOP demonstrated that a high composite AHO score was correlated with lowered IOP (Tukey-Kramer method p < 0.05). Additionally, it was found that if one of the three regions had an AHO grade of ≥ G2, an IOP of < 20 mmHg could be predicted. (Fischer's exact test p < 0.0001). Calculated speed was as follows: at G1, the speed was 0.68 ± 0.26 mm/s (n = 7), at G2, the speed was 1.8 ± 0.84 mm/s (n = 5), and at G3, the speed was 6.8 ± 3.3 mm/s (n = 6). CONCLUSION: There was a significant correlation between an increase in the composite AHO score and a decrease in IOP. Additionally, the speed of RBC clusters as they traveled through the ESVs remained consistent for each of the grades, and the span of the speeds from lower to higher grades represented a significant range. These findings suggest that the grading system is a reliable measure of AHO. TRIAL REGISTRATION IDENTIFIER: UMIN 000031745.

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.

Effects of Brinzolamide, a Topical Carbonic Anhydrase Inhibitor, on Corneal Endothelial Cells.

INTRODUCTION: This clinical study aimed to investigate the effect of brinzolamide, a topical carbonic anhydrase inhibitor, on corneal endothelial cells (CECs) in patients with glaucoma using a follow-up clinical study design. METHODS: Patients with primary open-angle glaucoma or ocular hypertension were administrated an ophthalmic solution of either latanoprost alone (LT) as a control (n = 18) or latanoprost plus brinzolamide (LT + BR; n = 16). CECs were examined at baseline and at 4, 12, 24, and 48 weeks in 18 and 16 eyes of the LT and LT + BR groups, respectively, using a non-contact specular microscope. CECs were evaluated by parameters, including cell density (CD), coefficient of variation (CV) in cell size, and percentage hexagonality (Hex). RESULTS: Compared with the baseline intraocular pressure (IOP), the mean IOP in the LT group was significantly reduced at 12 and 24 weeks, whereas that in the LT + BR group was significantly reduced at all time points (P < 0.01). The mean CD, CV, and Hex at baseline were not significantly different between the two groups. No significant time-course changes in CD, CV, or Hex were observed in either group. At 48 weeks, there was no significant difference in the mean CD, CV, or Hex between the two groups. CONCLUSION: Patients treated with LT + BR showed significant IOP reduction. However, the use of brinzolamide in addition to latanoprost had no influence on CECs during the one-year follow-up period.

Relationship between consecutive deterioration of mean deviation value and progression of visual field defect in open-angle glaucoma.

PURPOSE: To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma. PATIENTS AND METHODS: The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed. RESULTS: A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P<0.0001, Cochran-Armitage trend test). A significant association was observed for MD slope worsening in the eyes with three (odds ratio: 2.1, P=0.0224) and four (odds ratio: 3.6, P=0.0008) consecutive deterioration of MD value in multiple logistic regression analysis, but no significant association in the eyes with two consecutive deterioration (odds ratio: 1.1, P=0.8282). The eyes with VF progression had significantly lower intraocular pressure reduction rate (P<0.01). CONCLUSION: This retrospective study has shown that three or more consecutive deterioration of MD value might be a predictor to future significant MD slope worsening in OAG.

Relationship between progression of visual field defect and intraocular pressure in primary open-angle glaucoma.

PURPOSE: To analyze the relationship between intraocular pressure (IOP) and the progression of visual field defects in Japanese primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG) patients. PATIENTS AND METHODS: The subjects of the study were patients undergoing treatment for POAG or NTG who had performed visual field tests at least ten times with a Humphrey field analyzer (Swedish interactive thresholding algorithm standard, C30-2 program). The progression of visual field defects was defined by a significantly negative value of the mean deviation slope at the final visual field test during the follow-up period. The relationships between the progression of visual field defects and IOP, as well as other clinical factors, were retrospectively analyzed. RESULTS: A total of 156 eyes of 156 patients were included in the analysis. Significant progression of visual field defects was observed in 70 eyes of 70 patients (44.9%), while no significant progression was evident in 86 eyes of 86 patients (55.1%). The eyes with visual field defect progression had significantly lower baseline IOP (P<0.05), as well as significantly lower IOP reduction rate (P<0.01). The standard deviation of IOP values during follow-up was significantly greater in the eyes with visual field defect progression than in eyes without (P<0.05). CONCLUSION: Reducing IOP is thought to be useful for Japanese POAG or NTG patients to suppress the progression of visual field defects. In NTG, IOP management should take into account not only achieving the target IOP, but also minimizing the fluctuation of IOP during follow-up period.

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.

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.

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.

Efficacy and safety of tafluprost in normal-tension glaucoma with intraocular pressure of 16 mmHg or less.

PURPOSE: To evaluate the intraocular pressure (IOP)-reducing effects and safety of 0.0015% tafluprost ophthalmic solution (tafluprost) in normal-tension glaucoma (NTG) patients with an IOP of 16 mmHg or less. METHODS: NTG patients with a baseline IOP of 16 mmHg or less were enrolled for a one-eye study in which tafluprost was applied once daily for 12 weeks. The presence of adverse drug reactions and the cumulative incidence of adverse events were also investigated. RESULTS: Among the 44 enrolled patients, 41/44 (93.2%) eyes completed the study. The baseline IOP was 13.2 ± 1.3 mmHg in the study eyes and 13.0 ± 1.3 mmHg in the fellow eyes, which was not statistically significant (P = 0.9173, Student's t test). The values obtained for IOP in the study eyes versus fellow eyes were 10.2 ± 1.6 versus 12.1 ± 1.5 mmHg at week 12. The IOP difference between the study eyes and the fellow eyes was statistically significant (P < 0.0001, Student's t test). The cumulative incidence of adverse events was 58.5% by week 12. Ocular itching was the most frequently observed adverse event (29.3%). All adverse events were clinically tolerable. CONCLUSIONS: Tafluprost induced significant IOP reductions in NTG patients with a baseline IOP of 16 mmHg or less without raising any safety concerns.

[Anderson criteria in early glaucomatous visual field defects with the SITA Standard].

PURPOSE: We evaluated the positive rate of the Anderson criteria of suspected early glaucomatous visual field defects (GVFDs). SUBJECTS AND METHODS: Ninety-six eyes of 96 patients, who had suspected primary open-angle glaucoma with apparent glaucomatous optic disc changes and who had more than -6.0 dB of mean deviation (MD) with Swedish Interactive Thresholding Algorithm Standard (SITA-S) Central 30-2 program in the Humphrey Field Analyzer, were selected. We applied the Anderson criteria and calculated the positive rates for these criteria and for three elements pattern deviation probability plots (PD plots), glaucoma hemifield test (GHT), pattern standard deviation (PSD). RESULTS: The positive rate of the Anderson criteria was 78.1% and the PD plots (77.1%) were significantly higher rate than the GHT (62.5%) or the PSD (63.5%). The positive rate of the Anderson criteria was 100% in the MD of less than -3.0 dB and was 65.6% even in the MD of more than -3 dB (p < 0.0001). On the other hand, 57.9% of the eyes with an MD between -2 dB and -1 dB showed positive in all elements. At more than -1.0 dB of MD, the PD plots (50.0%) were significantly higher than the PSD (18.8%) or the GHT (21.9%) (PSD: p = 0.0085, GHT : p = 0.0190). CONCLUSION: Using the SITA-S, the Anderson criteria showed a high positive rate in eyes with suspected early GVFDs.

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

PURPOSE: To 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). METHODS: Patients 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. RESULTS: Of 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. CONCLUSION: Switching to TRV improved SPK observed in a population using LAT, likely because of a decrease in exposure to BAC.

[Retinopathy of prematurity in extremely low birth weight infants: a Tokyo multicenter study].

OBJECTIVE: To investigate how the increase in survival rate in extremely low birth weight (a birth weight of 1,000 g or less) infants had affected the incidence of retinopathy of prematurity (ROP) and the frequency of laser treatment. METHODS: We retrospectively reviewed the medical records of 122 surviving premature infants with birthweights less than 1,000 g to determine the severity of ROP observed at 16 neonatal intensive care units in Tokyo between April and October 2002. RESULTS: The survival rate was 85.6%. The mean gestational age was 26.74 weeks and the mean birth weight was 782.25 g. One-hundred-and-five infants (86.1%) developed ROP, fifty (41.0%) received laser treatment, and six (4.9%) had retinal detachment. The median postmenstrual age (gestational age at birth plus chronological age in weeks, PMA) at the onset of ROP was 32.5 weeks, and the first laser treatment was performed at the median PMA of 35.7 weeks. CONCLUSIONS: In these extremely low birth weight infants, there was an increase in the survival rate and in the incidence of severe ROP that progressed to the stage that required treatment.