Efficacy and safety of first-line or second-line selective laser trabeculoplasty for normal-tension glaucoma: a multicentre cohort study.

BACKGROUND/AIMS: This study aimed to investigate and compare the efficacy and safety of first-line and second-line selective laser trabeculoplasty (SLT) in Japanese patients with normal-tension glaucoma (NTG). METHODS: 100 patients with NTG were enrolled in this study. Patients were treated with SLT as a first-line or second-line treatment for NTG. Main outcome measures were intraocular pressure (IOP) reduction rate, outflow pressure improvement rate (ΔOP), success rate at 1 year and complications. Success was defined as ΔOP≥20% (criterion A) or an IOP reduction ≥20% (criterion B) without additional IOP-lowering eye-drops, repeat SLT or additional glaucoma surgeries. The incidence of transient IOP spike (>5 mm Hg from the pretreatment IOP), conjunctival hyperaemia, inflammation in the anterior chamber and visual impairment due to SLT were assessed. RESULTS: A total of 99 patients (99 eyes) were initially enrolled in this study, including 74 eyes assigned to the first-line SLT group and 25 eyes to the second-line SLT group. The mean IOP of 16.3±2.1 mm Hg before SLT decreased by 17.1%±9.5% to 13.4±1.9 mm Hg at 12 months after SLT in the first-line group (p<0.001), and the mean IOP of 15.4±1.5 mm Hg before SLT decreased by 12.7%±9.7% to 13.2±2.0 mm Hg at 12 months after SLT (p=0.005) in the second-line group. Both groups showed significant reductions in IOP. Higher pre-SLT IOP and thinner central corneal thickness were associated with greater IOP reduction. The success rate at 1 year was higher in the first-line compared with the second-line group, with lower pretreatment IOP and the use of IOP-lowering medication before SLT being associated with treatment failure. Most post-treatment complications were minor and transient. CONCLUSIONS: SLT may be an effective and safe treatment option for NTG, as either a first-line or second-line treatment. TRIAL REGISTRATION NUMBER: The study was registered in the UMIN-CTR (UMIN Test ID: UMIN R000044059).

Comparison of surgical outcomes between iStent inject W implantation and microhook ab interno trabeculotomy in combination with phacoemulsification in primary open-angle glaucoma patients.

Purpose: To examine primary open-angle glaucoma patients after undergoing combined cataract surgery with microhook ab interno trabeculotomy (µLOT-Phaco) or iStent inject W implantation (iStent-Phaco), and then evaluate the surgical outcomes after a minimum of 6 months of follow-up. Methods: Between October 2020 and July 2022, 39 µLOT-Phaco eyes and 55 iStent-Phaco eyes that underwent surgery were evaluated in this retrospective, multicenter comparative case series. Data that included preoperative and postoperative intraocular pressure (IOP), number of glaucoma medications, and occurrence of complications were collected from medical records and then examined. Surgical failure was defined as patients exhibiting a < 20% reduction in the preoperative IOP or an IOP > 18 mmHg on two consecutive follow-up visits, or when patients were required to undergo reoperation. Success rates were determined based on a Kaplan-Meier survival analysis. Results: At 3, 6 and 12 months postoperatively, there was a significant postoperative reduction in the IOP (p < 0.001) and in the medications scores (p < 0.001) for both of the groups. In the µLOT-Phaco and iStent-Phaco groups, the probabilities of success at 6 and 12 months were 55.3 and 45.5%, and 48.4 and 45.5% (p = 0.38; log-rank test), respectively. In the iStent-Phaco group, there was a significant decrease in the hyphema. Conclusion: Comparable surgical outcomes occurred for both the µLOT and iStent inject W procedures.

Additive effects of brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination in prostaglandin analog-treated Japanese glaucoma patients.

PURPOSE: A brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination (BBFC) was recently approved for glaucoma and ocular hypertension treatment in Japan. We investigated the efficacy and safety of BBFC used concomitantly with prostaglandin analogs (PG) or a PG/beta-blocker fixed-dose combination (PG/beta FC). STUDY DESIGN: This was a prospective, open-label, multicenter study. PATIENTS AND METHODS: We enrolled Japanese patients with open-angle glaucoma. BBFC (Ailamide) was concomitantly administered to either the PG or the PG/beta FC group, and intraocular pressure (IOP) and safety were evaluated at 4 and 12 weeks. The groups were stratified into low and high IOP baseline groups based on the median baseline IOP. RESULTS: We enrolled 100 patients, 91 of whom completed the 12-week follow-up. The mean ages were 67.1 and 65.7 years in the PG group (n = 45, baseline IOP of 15.7 ± 2.3 mmHg) and the PG/beta FC group (n = 46, baseline IOP of 16.3 ± 2.3 mmHg), respectively. After BBFC administration, IOPs at 4 and 12 weeks were 13.0 ± 2.0 and 13.0 ± 2.6 mmHg (P < 0.0001) in the PG group, respectively, and 13.7 ± 2.4 and 13.7 ± 2.2 mmHg (P < 0.0001) in the PG/beta FC group, respectively. IOP decreased by - 2.0 ± 1.8 mmHg (P < 0.0001) and -1.9 ± 1.4 mmHg (P < 0.0001) in the low baseline PG group (14.1 mmHg) and low baseline PG/beta FC group (14.8 mmHg) at 12 weeks, respectively. Sixteen adverse events were identified, all of which were common and did not affect visual acuity. CONCLUSIONS: BBFC can be used concomitantly with PG or PG/beta FC to reduce IOP without serious complications.

Noninferiority of Microhook to Trabectome: Trabectome versus Ab Interno Microhook Trabeculotomy Comparative Study (Tram Trac Study).

PURPOSE: To elucidate the noninferiority of ab interno microhook trabeculotomy (µTLO) using a recently developed reusable stainless spatula-type microhook device to incise the trabecular meshwork to Trabectome (Neomeix, Inc) surgery in terms of the 1-year postoperative outcomes of Japanese patients with glaucoma by means of propensity score analyses. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: We enrolled 553 and 392 patients who underwent Trabectome surgery and µTLO, respectively, between January 2014 and March 2020 at 10 facilities. METHODS: Logistic regression analysis was conducted to calculate the propensity score, which indicates the likelihood of treatment assignment (Trabectome or µTLO). We set the following factors as outcome-related covariates: age, sex, facility, glaucoma disease types, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation of Humphrey visual field test results, antithrombotic drug use, the presence or absence of combined cataract surgery, and incision range of the trabecular meshwork (1 or 2 quadrants). We analyzed 4 different methods (matching, inverse probability of treatment weighting [IPTW], stratification, and regression adjustment) using the propensity score. We set 15% as the noninferiority margin based on previous Trabectome meta-analysis results. MAIN OUTCOME MEASURES: The primary outcome was surgical success at 1 year after surgery. We defined surgical success as satisfying all 3 criteria: (1) IOP within 5 to 21 mmHg, (2) IOP reduction of 20% or more from preoperative IOP, and (3) no additional glaucoma surgery. RESULTS: The 95% confidence interval of risk difference of surgical failure in µTLO in reference to Trabectome surgery was -12.1% to +9.5% in matching, -12.7% to +11.1% in IPTW, -12.2 to +7.0 in stratification, and -9.7% to +8.1% in regression adjustment, all of which fell within the predetermined noninferiority margin of 15%. CONCLUSIONS: Surgical success of µTLO at 1 year after was not inferior to that of Trabectome surgery.

Stratification-Based Investigation of Adjunctive Brimonidine or Timolol to a Prostaglandin Analogue in Japanese Patients with Normal-Tension Glaucoma.

PURPOSE: We previously investigated the efficacy and safety of adding 0.1% brimonidine (Brim) or 0.5% timolol (Tim) to prostaglandin analogue (PGA) monotherapy to treat patients with normal-tension glaucoma (NTG) with intraocular pressure (IOP) of ≤16 mmHg. Herein, we describe an additional post-hoc stratifying analysis of the possible differences in the effect of IOP-lowering and pulse rate (PR) after adjunctive Brim or Tim to PGA. PATIENTS AND METHODS: This study included 128 subjects. Patients with NTG treated with PGA were stratified based on their baseline IOP. The changes in IOP from baseline and the effect of patient factors on IOP changes were investigated. Patients were stratified by age for investigation of their PR and blood pressure (BP). The change and the effect of patient factors on PR and BP were investigated. RESULTS: After stratification analysis, in 52 eyes treated with Brim and 61 eyes with Tim with baseline IOP 12 ≤ IOP ≤ 16 mmHg, both eye drops lowered IOP significantly (P < 0.0001), and the IOP-lowering efficacy of Brim was non-inferior to that of Tim. However, in 9 Brim- and 6 Tim-treated eyes with baseline IOP of <12 mmHg, no statistically significant decrease in IOP was evident with either eye drop. In the Tim group, PR decreased significantly (P < 0.05) after stratification by age. CONCLUSION: The IOP-lowering efficacy of Brim was non-inferior to that of Tim after stratification by baseline IOP (12 ≤ IOP ≤ 16 mmHg). The discrepancy in the IOP-lowering effects of Brim and Tim observed in the previous study was thought to be related to enrolled subjects with low baseline IOP. PR decreased significantly in the Tim group even after age stratification. PR should be considered when selecting ß-blockers for glaucoma treatment.

Comparisons between retinal vessel calibers and various optic disc morphologic parameters with different optic disc appearances: The Glaucoma Stereo Analysis Study.

The Glaucoma Stereo Analysis Study (GSAS) is a multicenter collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. This study evaluated the retinal vessel calibers and correlations using GSAS fundus photographs between retinal vessels and 38 optic nerve head (ONH) morphologic parameters comprehensively. In all 240 eyes, the mean central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were 138.4 and 216.5 µm, respectively; the CRAE correlated with age, visual field scores and 19 ONH parameters and CRVE correlated with age, intraocular pressure, visual field scores and 11 ONH parameters. Among the different optic disc appearances including focal ischemia (FI) (n = 53, 22%), generalized enlargement (GE) (n = 53, 22%), myopic glaucoma (MY) (n = 112, 47%), and senile sclerosis (SS) (n = 22, 9%), the CRAE did not differ significantly; CRVE was significantly narrower in SS than in FI and MY. In FI, GE, MY, and SS disc types, CRAE correlated with 3, 14, 9, and 2 ONH parameters, respectively, and CRVE corelated with 9, 0, 12, and 6 ONH parameters, respectively. We confirmed previous observations on the effect of retinal vessel narrowing on glaucomatous changes in the ONH and visual field. The associations between retinal vessel caliber and ONH morphologic parameters vary among different optic disc appearances, suggesting different effects of vascular changes in each disc type.

Intraobserver and interobserver agreement among anterior chamber angle evaluations using automated 360-degree gonio-photos.

PURPOSE: To investigate the reproducibility for the iridocorneal angle evaluations using the pictures obtained by a gonioscopic camera, Gonioscope GS-1 (Nidek Co., Gamagori, Japan). METHODS: The pragmatic within-patient comparative diagnostic evaluations for 140 GS-1 gonio-images obtained from 35 eyes of 35 patients at four ocular sectors (superior, temporal, inferior, and nasal angles) were conducted by five independent ophthalmologists including three glaucoma specialists in a masked fashion twice, 1 week apart. We undertook the observer agreement and correlation analyses of Scheie's angle width and pigmentation gradings and detection of peripheral anterior synechia and Sampaolesi line. RESULTS: The respective Fleiss' kappa values for the four elements between manual gonioscopy and automated gonioscope by the glaucoma specialist were 0.22, 0.40, 0.32 and 0.58. Additionally, the respective intraobserver agreements for the four elements by the glaucoma specialist each were 0.32 to 0.65, 0.24 to 0.71, 0.35 to 0.70, and 0.20 to 0.76; the Fleiss' kappa coefficients for the four elements among the three glaucoma specialists were, respectively, 0.31, 0.38, 0.31, and 0.17; the Fleiss' kappa coefficients for the angle width and pigmentation gradings between the two glaucoma specialists each were 0.30 to 0.35, and 0.29 to 0.43, respectively. Overall, the Kendall's tau coefficients for the angle gradings reflected the positive correlations in the evaluations. CONCLUSION: Our findings suggested slight-to-substantial intraobserver agreement and slight-to-fair (among the three) or fair-to-moderate (between the two each) interobserver agreement for the angle assessments using GS-1 gonio-photos even by glaucoma specialists. Sufficient training and a solid consensus should allow us to perform more reliable angle assessments using gonio-photos with high reproducibility.

The usefulness of the Deep Learning method of variational autoencoder to reduce measurement noise in glaucomatous visual fields.

The aim of the study was to investigate the usefulness of processing visual field (VF) using a variational autoencoder (VAE). The training data consisted of 82,433 VFs from 16,836 eyes. Testing dataset 1 consisted of test-retest VFs from 104 eyes with open angle glaucoma. Testing dataset 2 was series of 10 VFs from 638 eyes with open angle glaucoma. A VAE model to reconstruct VF was developed using the training dataset. VFs in the testing dataset 1 were then reconstructed using the trained VAE and the mean total deviation (mTD) was calculated (mTDVAE). In testing dataset 2, the mTD value of the tenth VF was predicted using shorter series of VFs. A similar calculation was carried out using a weighted linear regression where the weights were equal to the absolute difference between mTD and mTDVAE. In testing dataset 1, there was a significant relationship between the difference between mTD and mTDVAE from the first VF and the difference between mTD in the first and second VFs. In testing dataset 2, mean squared prediction errors with the weighted mTD trend analysis were significantly smaller than those form the unweighted mTD trend analysis.

Usefulness of data augmentation for visual field trend analyses in patients with glaucoma.

AIM: To investigate the usefulness of data augmentation in visual field (VF) trend analyses in patients with glaucoma. METHOD: This study included 6380 VFs from 638 eyes of 417 patients with open-angle glaucoma. Various affine transformations were applied to augment the VF data: (1) rotation, (2) scaling, (3) vertical and horizontal shift and (4) a combination of these different transformations. Using pointwise linear regression (PLR), the total deviation (TD) values of a patient's 10th VF were predicted using TD values from shorter VF series (from first to third VFs (VF1-3) to first to ninth VFs (VF1-9)) with and without VF data augmentation, and the root mean squared error (RMSE) was calculated. RESULTS: With PLR, mean RMSE without VF augmentation averaged from 3.95 (VF1-3) to 19.01 (VF1-9) dB. The RMSE was significantly improved by applying the different transformations: (1) rotation (from VF1-3 to VF1-7), (2) scaling (from VF1-3 to VF1-6), (3) vertical and horizontal shifts (from VF1-3 to VF1-4) and (iv) a combination of these (from VF1-3 to VF1-7). Progression rates in VF1-10 had better agreement with those in shorter VF series when a combination of affine transformation was applied. The differences in rates were between 1.9 (VF1-3) and 0.39 (VF1-9) dB if augmentation was used, which was significantly smaller than that observed when augmentation was not applied (from 2.6 with VF1-3 to 0.26 dB with VF1-9). CONCLUSION: It is useful to apply VF data augmentation techniques when predicting future VF progression in glaucoma using PLR, especially with short VF series.

Validating the efficacy of the binomial pointwise linear regression method to detect glaucoma progression with multicentral database.

BACKGROUND/AIM: We previously reported the benefit of applying binomial pointwise linear regression (PLR: binomial PLR) to detect 10-2 glaucomatous visual field (VF) progression. The purpose of the current study was to validate the usefulness of the binomial PLR to detect glaucomatous VF progression in the central 24°. METHODS: Series of 15 VFs (Humphrey Field Analyzer 24-2 SITA-standard) from 341 eyes of 233 patients, obtained over 7.9±2.1 years (mean±SD), were investigated. PLR was performed by regressing the total deviation of all test points. VF progression was determined from the VF test points analyses using the binomial test (one side, p<0.025). The time needed to detect VF progression was compared across the binomial PLR, permutation analysis of PLR (PoPLR) and mean total deviation (mTD) trend analysis. RESULTS: The binomial PLR was comparable with PoPLR and mTD trend analyses in the positive predictive value (0.18-0.87), the negative predictive value (0.89-0.95) and the false positive rate (0.057-0.35) to evaluate glaucomatous VF progression. The time to classify progression with binomial PLR (5.8±2.8 years) was significantly shorter than those with mTD trend analysis (6.7±2.8 years) and PoPLR (6.6±2.7 years). CONCLUSIONS: The binomial PLR method, which detected glaucomatous VF progression in the central 24° significantly earlier than PoPLR and mTD trend analyses, shows promise for improving our ability to detect visual field progression for clinical management of glaucoma and in clinical trials of new glaucoma therapies.

Validation of formula-predicted glaucomatous optic disc appearances: the Glaucoma Stereo Analysis Study.

AIMS: The Glaucoma Stereo Analysis Study (GSAS) is a multicentre collaborative study of the characteristics of glaucomatous optic disc morphology using a stereo fundus camera. Using the GSAS dataset, we previously established a formula for predicting different appearances of glaucomatous optic discs, although the formula lacked validation in an independent dataset. In this study, the formula was validated in another testing dataset. SUBJECTS AND METHODS: Testing dataset contained three-dimensionally analysed optic disc topographic parameters from 93 eyes with primary open-angle glaucoma; six topographic parameters (temporal and nasal rim-disc ratios, mean cup depth, height variation contour, disc tilt angle and rim decentring absolute value) were used for predicting different appearances of glaucomatous optic discs. The agreement between grader-classified optic disc types, that is, focal ischemic (FI), generalized enlargement, myopic glaucomatous (MY), and senile sclerotic (SS) and formula-predicted optic disc types, that is, pFI, pGE, pMY and pSS, were assessed. RESULTS: Based on this formula, the eyes were classified with pFI (21 eyes, 22.6%), pGE (27 eyes, 29.0%), pMY (26 eyes, 28.0%) and pSS (19 eyes, 20.4%) when the top predictive element based on the formula was considered as the optic disc appearance in each eye. The six topographic parameters used in the formula differed significantly among the four predicted optic disc types. Substantial agreement (κ = 0.7496) was seen for the top two predictive elements based on the formula that agreed with the graders' classification in 76 (81.7%) eyes. Among the four optic disc types, the levels of agreement were relatively lower in the SS type (κ = 0.3863-0.5729) compared with the other three optic disc types (κ = 0.7898-0.8956) even though the unclassifiable and mixed optic disc types were excluded from the testing dataset. CONCLUSION: The GSAS classification formula can predict and quantify each component of different optic disc appearances in each eye and provide a novel parameter to describe glaucomatous optic disc characteristics.

Comparison of success rates in eye drop instillation between sitting position and supine position.

PURPOSE: To compare the success rates of eye drop instillation in the sitting position and supine position among Japanese patients with ocular diseases (cataract, glaucoma, or retinal and vitreous diseases). METHODS: Patients who were hospitalized in Okayama University Hospital for eye surgery were studied. Instillation procedures of each patient in both the sitting and supine positions were recorded using a video camera at the time of instillation. We defined "success" when one drop fell accurately onto the ocular surface at the first attempt. Instillation of two or more drops, drops delivered to a site other than the eye surface, and touching the eyelashes, eyelids, or conjunctiva with the tip of the eye drop bottle were regarded as "failure". We excluded patients with vision below counting finger. RESULTS: One-hundred and two patients (54 males and 58 females, aged 70.2 ± 12.3 years) with ocular disease who were hospitalized for surgery (cataract: 61.8%, glaucoma: 15.7%, retinal and vitreous diseases: 22.5%) were included in this prospective observational study. The mean duration of eye drop use was 3.1 ± 5.2 years. The success rate of eye drop instillation was significantly higher in the supine position than in the sitting position (64.7% vs. 50%, P = 0.0039). The mean age was significantly higher in the failure group than in the success group (74.0 ± 11.5 vs. 67.7 ± 12.4 years, P = 0.0085) for the sitting position, but not significantly different for the supine position (72.3 ± 12.9 vs. 70.1 ± 12.0 years, P = 0.3849). No significant differences in mean duration of drop use, mean corrected VA, and mean spherical equivalent refraction were observed between success and failure groups, for both sitting and supine positions. CONCLUSIONS: In the present study, the success rate of eye drop instillation was significantly higher when applied in the supine position than in the sitting position.

Validating Variational Bayes Linear Regression Method With Multi-Central Datasets.

Purpose: To validate the prediction accuracy of variational Bayes linear regression (VBLR) with two datasets external to the training dataset. Method: The training dataset consisted of 7268 eyes of 4278 subjects from the University of Tokyo Hospital. The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG) dataset consisted of 271 eyes of 177 patients, and the Diagnostic Innovations in Glaucoma Study (DIGS) dataset includes 248 eyes of 173 patients, which were used for validation. Prediction accuracy was compared between the VBLR and ordinary least squared linear regression (OLSLR). First, OLSLR and VBLR were carried out using total deviation (TD) values at each of the 52 test points from the second to fourth visual fields (VFs) (VF2-4) to 2nd to 10th VF (VF2-10) of each patient in JAMDIG and DIGS datasets, and the TD values of the 11th VF test were predicted every time. The predictive accuracy of each method was compared through the root mean squared error (RMSE) statistic. Results: OLSLR RMSEs with the JAMDIG and DIGS datasets were between 31 and 4.3 dB, and between 19.5 and 3.9 dB. On the other hand, VBLR RMSEs with JAMDIG and DIGS datasets were between 5.0 and 3.7, and between 4.6 and 3.6 dB. There was statistically significant difference between VBLR and OLSLR for both datasets at every series (VF2-4 to VF2-10) (P < 0.01 for all tests). However, there was no statistically significant difference in VBLR RMSEs between JAMDIG and DIGS datasets at any series of VFs (VF2-2 to VF2-10) (P > 0.05). Conclusions: VBLR outperformed OLSLR to predict future VF progression, and the VBLR has a potential to be a helpful tool at clinical settings.

Effect of Botulinum Toxin A Treatment on Eyelid Pressure in Eyes with Blepharospasm.

OBJECTIVE: To determine the effect of botulinum toxin A (BTX-A) on the eyelid pressure in patients with benign essential blepharospasm (BEB). METHODS: Twenty normal volunteers (10 men, 10 women; average age 59.7 ± 11.3 years) and 33 patients (12 men, 21 women; average age 61.1 ± 14.7 years) with BEB were studied. The upper and lower eyelid pressures were measured with a blepharo-tensiometer in the normal subjects (N group). The eyelid pressures and intraocular pressures (IOP) were measured before and after the BTX-A injections in the BEB patients (B group). RESULTS: The mean eyelid pressure in the N group was 31.0 ± 6.8 mmHg for the upper eyelid and 29.9 ± 6.5 mmHg for the lower eyelid (P > 0.05). The mean eyelid pressure in the B group before treatment was 35.3 ± 7.0 mmHg for the upper eyelid and 37.8 ± 6.6 mmHg for the lower eyelid. The eyelid pressure in the B group was significantly higher than in the N group for the upper and lower eyelids (both P < 0.001). The eyelid pressure was significantly decreased after BTX-A treatment for the upper (29.9 ± 7.5 mmHg) and the lower (32.8 ± 7.0 mmHg) eyelids (both P < 0.001). The mean IOP was 15.1 ± 2.9 mmHg before, and it significantly decreased to 14.5 ± 2.8 mmHg (P = 0.020) after the BTX-A injections. The IOP was significantly correlated with the lower eyelid pressure (P = 0.0435), but not with the upper eyelid pressure (P = 0.175). CONCLUSION: The eyelid pressure was higher in the patients with BEB. The eyelid pressure and the IOP were significantly reduced after the BTX-A injections. In addition, the IOPs were significantly correlated with the eyelid pressure of the lower eyelid.

Factors affecting eye drop instillation in glaucoma patients with visual field defect.

BACKGROUND: To investigate the success rate of eye drop instillation in glaucoma patients with visual field defect as well as non-glaucoma volunteers. Factors that may affect the success rate of eye drop instillation were also evaluated. DESIGN: A prospective, observational study. PARTICIPANTS: Seventy-eight glaucoma patients and 85 non-glaucoma volunteers were recruited in this study. METHODS: Open angle glaucoma patients with visual field defect as well as non-glaucoma volunteers were asked to video record their procedures of eye drop instillation using a 5-mL plastic bottle of artificial tear solution. Success of eye drop instillation was judged on video based on the first one drop of solution successfully applied on the cornea, by two investigators. MAIN OUTCOME MEASURES: Success rate of eye drop instillation in glaucoma patients and non-glaucoma volunteers. Factors related to success rate of eye drop instillation, such as visual field defect and clinical characteristics, were also analyzed using multivariable logistic regression. RESULTS: No significant deference in mean age was observed between two groups (glaucoma: 64.5 ± 14.4 years, non-glaucoma: 60.9 ± 14.1 years, P = 0.1156). Success rate of eye drop instillation was significantly lower (P = 0.0215) in glaucoma patients (30/78; 38.5%) than in non-glaucoma volunteers (48/85; 56.5%). The most frequent reason of instillation failure in glaucoma patients was touching the bulbar conjunctiva, cornea, eyelid or eyelashes with the tip of the bottle (29.5%). Multivariable logistic regression analysis identified lower corrected visual acuity (VA) (≤ 1.0; odds ratio [OR] = 0.20, 95% confidence interval [CI] 0.04-0.93, P = 0.0411), lower mean deviation (MD) (< -12 dB; OR = 0.20, 95% CI 0.05-0.86, P = 0.0307) and visual field defect (VFD) in the inferior hemifield (OR = 0.11, 95% CI 0.02-0.34, P < 0.001) to be significantly related to instillation failure in glaucoma patients. CONCLUSIONS: Success rate of eye drop instillation was significantly lower in glaucoma patients than in non-glaucoma volunteers. Corrected VA ≤ 1.0, MD < -12 dB and/or VFD in the inferior hemifield may be related to failure of eye drop instillation.

Multicenter, Randomized, Investigator-Masked Study Comparing Brimonidine Tartrate 0.1% and Timolol Maleate 0.5% as Adjunctive Therapies to Prostaglandin Analogues in Normal-Tension Glaucoma.

INTRODUCTION: This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction. METHODS: In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit. RESULTS: A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (-1.05 ± 1.81 mmHg) and timolol (-1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [-0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively. CONCLUSION: This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate. FUNDING: Senju Pharmaceutical Co., Ltd. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier, UMIN000014810.

Investigating the usefulness of a cluster-based trend analysis to detect visual field progression in patients with open-angle glaucoma.

BACKGROUND/AIMS: To investigate the usefulness of the Octopus (Haag-Streit) EyeSuite's cluster trend analysis in glaucoma. METHODS: Ten visual fields (VFs) with the Humphrey Field Analyzer (Carl Zeiss Meditec), spanning 7.7 years on average were obtained from 728 eyes of 475 primary open angle glaucoma patients. Mean total deviation (mTD) trend analysis and EyeSuite's cluster trend analysis were performed on various series of VFs (from 1st to 10th: VF1-10 to 6th to 10th: VF6-10). The results of the cluster-based trend analysis, based on different lengths of VF series, were compared against mTD trend analysis. RESULT: Cluster-based trend analysis and mTD trend analysis results were significantly associated in all clusters and with all lengths of VF series. Between 21.2% and 45.9% (depending on VF series length and location) of clusters were deemed to progress when the mTD trend analysis suggested no progression. On the other hand, 4.8% of eyes were observed to progress using the mTD trend analysis when cluster trend analysis suggested no progression in any two (or more) clusters. CONCLUSION: Whole field trend analysis can miss local VF progression. Cluster trend analysis appears as robust as mTD trend analysis and useful to assess both sectorial and whole field progression. Cluster-based trend analyses, in particular the definition of two or more progressing cluster, may help clinicians to detect glaucomatous progression in a timelier manner than using a whole field trend analysis, without significantly compromising specificity.

Fixed combination of travoprost and timolol maleate reduces intraocular pressure in Japanese patients with primary open-angle glaucoma or ocular hypertension: analysis by prostaglandin analogue.

BACKGROUND: We have shown a decrease in mean intraocular pressure (IOP) by switching to travoprost/timolol fixed combination (TTFC) in subjects receiving prostaglandin analogue (PGA) monotherapy and requiring additional medication in a previous report. For analyzing factors affecting IOP reduction, baseline IOP and preceding PGA were selected as statistically and clinically significant factors. In this report, we examine IOP-lowering effect and adverse drug reactions by preceding PGA. METHODS: Patients with primary open angle glaucoma or ocular hypertension who received monotherapy with one of four PGAs (travoprost, latanoprost, tafluprost, or bimatoprost) for at least 3 months at 26 institutions and were determined to require additional medication by their primary physician were included. IOP reduction and adverse events were examined at 4, 8, and 12 weeks for each of four PGAs after switching to TTFC. RESULTS: In total, 157 patients who could be followed up for at least 4 weeks after switching to TTFC were included in the efficacy analysis. Multiple regression analysis was performed, and baseline IOP and PGA were found to be significant factors to IOP reduction. IOP reduction at week 12, adjusted with the regression model, was -3.5, -1.8, and -1.4 mmHg in the tafluprost, latanoprost, and travoprost groups, whereas it was -0.5 mmHg in the bimatoprost group. Along with differences in baseline IOP between groups, an IOP-lowering effect of >1 mmHg was noted in the tafluprost, latanoprost, and travoprost groups after the switch. IOP was maintained at 13.8-14.8 mmHg throughout the follow-up period. No serious adverse events or noteworthy issues were observed in any group after the switch. CONCLUSION: Clinically significant IOP-reducing effects of TTFC were observed in the latanoprost, travoprost, and tafluprost groups when switching from each PGA monotherapy, while there were some differences in effects between groups, with minimal safety concerns.