Contributing factors for intraocular pressure control in patients with mostly normal-tension glaucoma after initial Ex-PRESS drainage device implantation.

PURPOSE: To investigate the postoperative intraocular pressure (IOP) control and identify the factors associated with failure of initial Ex-PRESS surgery in patients with open-angle glaucoma for 3 years. METHODS: A total of 79 patients with medically uncontrolled open-angle glaucoma (55 normal-tension glaucoma and 24 primary open-angle glaucoma) were enrolled. All patients underwent Ex-PRESS implantation (including combined cataract surgery). The outcome measure was the survival rate using life table analysis, the failure was defined as IOP of > 18 mmHg (criterion A), > 15 mmHg (criterion B) or > 12 mmHg (criterion C) and/or IOP reduction of < 20% from baseline (each criterion) without any glaucoma medications. The Cox proportional hazards model was used to identify risk factors for IOP management defined as the above criterion.  RESULTS: The mean preoperative IOP was 19.3 ± 5.8 mmHg. At 36 months, the mean IOP was 11.8 ± 3.6 mmHg with a mean IOP change of 7.5 mmHg (reduction rate 39.0%). The cumulative probability of success was 58% (95%CI: 42-64%) (criterion A), 48% (95%CI: 37-59%) (criterion B) and 30% (95%CI: 20-40%) (criterion C). In multivariate analyses, factors that predicted poor IOP control included the intervention of bleb needling after 6 months after the surgery (HR: 2.43; 95%CI: 1.35-4.37; P = 0.032). Transient hypotony was observed in 4 patients. CONCLUSION: The implementation of bleb needling after Ex-PRESS surgery in the late postoperative period was suggested to be the main risk factor for achieving lower IOP.

Structure Function Relationships of Vessel Density and Retinal Nerve Fiber Layer Thickness in Early Glaucomatous Eyes With High Myopia.

Purpose: The purpose of this study was to evaluate the structure function relationship of circumpapillary vessel density (cpVD) with visual field sensitivity (VFS) and compare its characteristics with circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in early glaucomatous (EG) and normal eyes with and without high myopia (HM). Methods: Seventy-five EG (mean deviation > -6 dB) and 7 normal eyes with HM (axial length [AL] >26.5 mm) and 111 EG and 11 normal eyes without HM were enrolled in this retrospective cross-sectional study. All patients underwent circumpapillary optical coherence tomography (OCT) and OCT angiography (OCTA) scanning with the Cirrus HD-6000 with AngioPlex OCTA (Carl Zeiss Meditec, Dublin, CA, USA). Structure function correlations were determined by comparing global, superior, inferior, and Garway-Heath sectoral values for cpVD and cpRNFLT with its corresponding 24-2 and 10-2 VFS of Humphrey Visual Field (HFA) analyzer. Results: CpVD showed no significant correlations with AL except for the nasal sector (P = 0.044), whereas cpRNFLT demonstrated significant positive association with AL in the global (P = 0.024), nasal (P = 0.020), and temporal (P < 0.001) sectors. In HM eyes, global and sectoral cpVD significantly correlated with corresponding VFS in all 24-2/10-2 VF sectors (all P < 0.05). CpVD-VFS correlation was significantly stronger than cpRNFLT-VFS in the nasal sector of HM eyes (P = 0.002) and temporal and inferior temporal sector of eyes without HM (P = 0.008 and P = 0.042, respectively). Conclusions: In EG eyes with HM, cpVD was less affected by AL in comparison to cpRNFLT and cpVD-VFS correlation was significant in all 24-2/10-2 VF sectors. AL-associated advantages of cpVD-VFS over cpRNFLT-VFS were observed.

Changes in corneal endothelial cell density after initial Ex-PRESS drainage device implantation and its relating factors over 3 years.

BACKGROUND/OBJECTIVES: To investigate changes in corneal endothelial cell density (CECD) after initial Ex-PRESS surgery in Japanese patients with open-angle glaucoma (OAG) followed-up for 36 months. SUBJECTS/METHODS: Corneal specular microscopy was used to examine preoperative and postoperative (3, 6, 12, 24 and 36 months) CECD and CECD changes were analysed. Kaplan-Meier survival curve was used to examine CECD maintained at 95% level, and Cox proportional hazards model was used to detect the risk factors for CECD loss. Intraocular pressure (IOP) changes during the course were also examined. RESULTS: A total of 79 eyes of 79 patients (standalone surgery, 24 cases; combined cataract surgery, 55 cases) were investigated. Preoperative CECD (mean ± SD) was 2521 ± 305 cells/mm² and 2429 ± 366 (P = 0.003, adjusted for Bonferroni correction), 2462 ± 332 (P = 0.002), 2457 ± 317 (P < 0.001), 2433 ± 333 (P < 0.001), and 2387 ± 352 (P < 0.001) at 3, 6, 12, 24 and 36 months, respectively. The decrease rate was calculated as 1.8%/year. Further, 95% maintenance CECD at 36 months was 50.0% (95% confidence interval, 37.1-63.0%). Both univariate and multivariate Cox proportional hazard models showed that a low preoperative CECD was a significant risk factor for CECD loss. Baseline IOP of 19.3 ± 5.8 mmHg decreased at all measurement points (P < 0.001) after surgery. CONCLUSION: CECD after initial Ex-PRESS surgery in 36 months might not be clinically problematic. However, longer-term follow-up is necessary, and regular CECD measurement should be performed, especially in patients with low CECD.

Prostaglandin-Associated Periorbitopathy Symptom Alleviation After Switching Prostaglandin F Receptor Agonist to EP2 Receptor Agonist in Patients with Glaucoma.

Purpose: Prostaglandin-associated periorbitopathy in patients with glaucoma is reportedly not caused by EP2 agonist, but it has been a cosmetic problem with prostaglandin F receptor (FP) agonists. In this study, patients with prostaglandin-associated periorbitopathy on FP agonists were switched to EP2 agonist and changes were investigated. Methods: Patients complaining of prostaglandin-associated periorbitopathy were included. The FP agonist was switched to EP2 agonist (omidenepag isopropyl), and patients were followed up for 7 months. Frontal photographs were taken at every visit, and objective changes in deepening of the upper eyelid sulcus were assessed by three observers. Subjective questionnaires (self-awareness of deepening of the upper eyelid sulcus, eyelid/peri-eyelid skin pigmentation, eyelash elongation, and conjunctival hyperemia) were acquired at the start and the endpoint. Factors associated with the change of prostaglandin-associated periorbitopathy were investigated using logistic regression analysis. Results: Included were 23 eyes of 23 patients (17 women; 60.6 years). At 7 months, objective deepening of the upper eyelid sulcus improved by 76%. The subjective questionnaires showed that deepening of the upper eyelid sulcus improved in 95%, eyelid/peri-eyelid skin pigmentation in 76%. The less extent of myopia was a significant factor in the eyes with improved eyelid/peri-eyelid skin pigmentation. After switching, no change in intraocular pressure or visual acuity was observed (P ≥ 0.22). Conclusion: Switching to omidenepag isopropyl increased patient satisfaction and might be the first step to lightening deepening of the upper eyelid sulcus and eyelid/peri-eyelid skin pigmentation. It was suggested that pigmentation may be more easily improved in nonmyopic eyes.

Newly or switching effect of a selective EP2 agonist on intraocular pressure in Japanese patients with open-angle glaucoma.

PURPOSE: To evaluate omidenepag isopropyl (OMDI) for its efficacy in intraocular pressure control (IOP) and adverse reactions following administrations in Japanese patients with open-angle glaucoma (OAG) over a 3-month period. STUDY DESIGN: Retrospective observational study. SUBJECTS AND METHODS: Group 1 included untreated OAG patients, Group 2 included OAG patients treated with prostaglandin F (FP) receptor agonists (monotherapy) and Group 3 included OAG patients treated with multidrug therapy, including FP receptor agonists. OMDI was newly administered in Group 1, and FP receptor agonists were switched to OMDI in Group 2. In Group 3, all other ocular hypotensive medications were continued except FP receptor agonists. IOP changes were examined, and adverse reactions were retrieved from the medical records. RESULTS: Group 1 included 32 eyes, Group 2, 20 eyes and Group 3, 17 eyes. In Group 1, the baseline IOP was 15.7 mmHg (95% confidence interval [CI] 14.7-16.8 mmHg). After eyedrop treatment, the IOP was 14.1 mmHg (P < 0.001) at 1 month and 13.7 mmHg (P < 0.001) at 3 months. By contrast, in Group 2 and Group 3, switching FP receptor agonists to OMDI did not result in significant IOP changes (P ≥ 0.71). Six patients developed adverse reactions (hyperemia, headache, ocular pain, and swollen eyelids). CONCLUSIONS: New administration of OMDI significantly reduced the IOP. Furthermore, the IOP did not change after switching from FP receptor agonists to OMDI, including multidrug therapy. OMDI can be used as a first-line drug and is comparable to FP receptor agonists in Japanese patients with OAG.

Diagnostic ability and sectoral structure-function relationship of circumpapillary and macular superficial vessel density in early glaucomatous eyes.

This study aimed to evaluate the diagnostic ability and sectoral structure function relationship of circumpapillary vessel density (cpVD) and macular vessel density (mVD) with optical coherence tomography angiography (OCTA) in early glaucomatous (EG) eyes. 224 EG eyes of 167 patients (mean deviation (MD) > - 6 dB) and 70 normal eyes of 70 subjects were enrolled in this retrospective cross-sectional study. All patients underwent OCT and OCTA scanning. Diagnostic abilities were evaluated with area under receiver operating characteristic curves (AUROC). Structure function relationships of superior, inferior and Garway-Heath sectoral values with its corresponding visual field (VF) sensitivity were determined using linear mixed models. AUROCs were 0.798, 0.621, 0.876 and 0.835 for cpVD, mVD, circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell-inner plexiform layer, respectively. AUROC of cpVD was significantly lower than cpRNFLT (P = 0.010) and higher than mVD (P < 0.001). All Garway-Heath sectors of cpVD significantly correlated with its corresponding VF sensitivity except for the nasal sector. MVD also showed significant structure function relationship and the correlations were stronger in the perifoveal region (6 mm annulus) than in the parafoveal region (3 mm annulus). CpVD demonstrated moderate diagnostic ability and both cpVD and mVD demonstrated significant association with VF sensitivity in EG eyes.

Long-term results of the safety and effectiveness of a novel microshunt in Japanese patients with primary open-angle glaucoma.

PURPOSE: To evaluate the long-term safety and effectiveness of the Preserflo MicroShunt in Japanese primary open-angle glaucoma (POAG) patients. STUDY DESIGN: Single-site, nonrandomized observational study. PATIENTS AND METHODS: Eight eyes of 7 POAG patients were included. The surgical complications and interventions were monitored. The preoperative and postoperative intraocular pressures (IOPs), numbers of antiglaucoma medications, logarithm of the minimum angle of resolution visual acuity (VA), mean deviation (MD) slope, and corneal endothelial cell density (CECD) were compared retrospectively. RESULTS: The mean follow-up period was 68.9 months (range, 48-76 months). The baseline IOP of 17.9 ± 3.5 mmHg and the number of glaucoma medications of 3.5 ± 0.5 were significantly reduced at subsequent follow-up visits. At 1, 2, 3, 4, 5, and 6 years postoperatively, the IOPs were 13.8 ± 2.9, 12.8 ± 2.3, 12.1 ± 3.2, 12.6 ± 2.5, 12.3 ± 1.0, and 13.5 ± 3.1 mmHg, respectively, with the use of 1.6 ± 1.4, 1.6 ± 1.6, 1.5 ± 1.4, 1.5 ± 1.4, 1.9 ± 1.3, and 2.0 ± 1.1 medications. Postoperative transient hyphema occurred in 1 eye. Postoperative needling was required in 5 eyes, 12 times in total. No eyes showed significant VA decline, except for 1 eye with a severe central visual field defect that existed preoperatively. The preoperative MD slope of - 1.6 ± 1.2 dB/year improved significantly, to - 0.3 ± 0.2 dB/year (P = 0.023), postoperatively. The baseline CECD decreased from 2595 ± 292 to 2478.4 ± 255 postoperatively. CONCLUSION: The microshunt surgical procedure is safe and effective for Japanese POAG patients.

Recovery of deepening of the upper eyelid sulcus after switching from prostaglandin FP receptor agonists to EP2 receptor agonist: a 3-month prospective analysis.

PURPOSE: To examine the effect of switching from a prostanoid FP receptor agonists to EP2 receptor agonist (omidenepag isopropyl) on the deepening of the upper eyelid sulcus (DUES) and intraocular pressure (IOP) in Japanese glaucoma patients over 3 months post treatment. STUDY DESIGN: Prospective observational study. METHODS: Patients with glaucoma who received FP receptor agonists treatment and had complained of DUES-related reduction in quality of life were included. Their FP receptor agonists was switched to omidenepag isopropyl without a drug holiday. At baseline and 1 and 3 months post-switch, photographs were taken and the changes in DUES were assessed by three independent observers. IOP and adverse events were also assessed. RESULTS: The study included 23 eyes of 23 patients (6 men, 17 women; average age, 60.6 years). After switching, DUES improved in 12 eyes at 1 month and in 16 eyes at 3 months; eyes in the remaining patients showed no worsening of the condition. The mean IOP before switching was 15.3 ± 3.3 mmHg (95% confidence interval 13.9-16.7 mmHg). Following the switch, the mean IOP values were 15.6 ± 3.3 mmHg (14.1-17.0 mmHg) at 1 month and 15.5 ± 3.3 mmHg (14.1-16.9 mmHg) at 3 months (P = 1.0 at 1 month, P = 1.0 at 3 months; both adjusted by Bonferroni correction). No adverse effects were observed. CONCLUSION: Omidenepag isopropyl improved DUES while maintaining IOP in over 70% of Japanese patients with glaucoma who exhibited DUES caused by FP receptor agonists; the improvement was observed within 3 months after switching from FP receptor agonists.

The Additive Effect of ROCK Inhibitor on Prostaglandin-Treated Japanese Patients with Glaucoma Indicating 15 mmHg and Under: ROCK U-15.

INTRODUCTION: We aimed to evaluate the additional effects and safety of a Rho-associated protein kinase (ROCK) inhibitor, ripasudil hydrochloride hydrate, in Japanese patients with primary open-angle glaucoma (POAG) with an intraocular pressure (IOP) of at most 15 mmHg undergoing prostaglandin F2α (FP) receptor agonist monotherapy (FP monotherapy). METHODS: In this prospective observational study, 30 Japanese patients with POAG and IOP of at most 15 mmHg (mean age 59.4 years; 10 men) who were undergoing FP monotherapy in both eyes were administered an additional dose of ripasudil hydrochloride hydrate (GLANATEC ophthalmic solution 0.4%: ripasudil) in one eye. The following factors were investigated at 1 and 3 months after the initiation of ripasudil treatment: (1) magnitude of change in IOP between the treated and contralateral untreated eyes, (2) number of treated eyes showing 20% and 30% IOP reduction, (3) IOP difference between treated and contralateral untreated eyes, and (4) safety during the treatment period. Both (1) and (3) were analyzed using the mixed-effect model for repeated measurements. RESULTS: The treated eyes showed significant reduction in IOP at 1 month (- 1.92 mmHg, P < 0.001) and 3 months (- 1.81 mmHg, P < 0.001). In contrast, contralateral untreated eyes did not show IOP reduction at 1 month (0.53 mmHg, P = 0.016) and 3 months (0.38 mmHg, P = 0.15). IOP reduction of - 20% and - 30% was achieved in 9 (30%) and 3 (10%) treated eyes, respectively. There were significant differences in IOP between the treated and contralateral untreated eyes at 1 month (- 2.46 mmHg, P < 0.001) and 3 months (- 2.20 mmHg, P < 0.001). Two patients experienced local adverse events (facial edema, one patient at week 1; blepharitis, one patient at 1 month); they recovered quickly after stopping ripasudil administration. CONCLUSION: In patients with POAG with an IOP of at most 15 mmHg undergoing FP monotherapy, the addition of ripasudil resulted in significant IOP lowering at 1 and 3 months. Ripasudil could be used to enhance the outcome of FP monotherapy. TRIAL REGISTRATION: Registered UMIN ID: UMIN000030742.

Central visual field change after fornix-based trabeculectomy in Japanese normal-tension glaucoma patients managed under 15 mmHg.

PURPOSE: To investigate how the central visual field would be changed after fornix-based trabeculectomy with mitomycin C in Japanese normal-tension glaucoma (NTG) patients monitored for more than 10 years including before surgery. METHODS: This is a retrospective cohort study. We identified twenty-eight eyes of 28 NTG cases regularly monitored for more than 5 years and examined static visual field (VF) tests for more than five times before and after fornix-based trabeculectomy (including combined surgery). Based on preoperative data for 6.3 years, we evaluated postoperative changes for 6.0 years in 10-2 VF and 30-2 VF. RESULTS: Six patients were male and 22 females, the mean age was 57.9 years, and the mean deviation was - 13.7 decibels. After surgery, mean IOP decreased from 13.9 to 9.0 mmHg (P ≤ 0.01), and medication score also did. The rate of 10-2 VF deterioration was significantly suppressed from - 1.0 dB/year preoperatively to - 0.4 dB/year postoperatively (P ≤ 0.01). And when 30-2 VF was divided into six relevant sectors, the rate of deterioration at cecocentral and arcuate areas of the superior hemifield was suppressed postoperatively (P ≤ 0.01 and P = 0.042, respectively). CONCLUSION: Based on long-term preoperative data, a significant positive change in 10-2 VF was observed after fornix-based trabeculectomy with mitomycin C in Japanese NTG patients with a mean IOP of 13.9 mmHg. Central vision could be expected to be maintained for NTG patients even if its preoperative IOP is low after successful trabeculectomy.

Evaluation of fornix-based trabeculectomy outcomes in Japanese glaucoma patients based on concrete long-term preoperative data.

PURPOSE: To investigate the outcomes of fornix-based trabeculectomy in Japanese patients with glaucoma based on more than five years of preoperative data. STUDY DESIGN: Retrospective case series METHODS: This study consisted of 35 eyes of 35 Japanese glaucoma patients (mean age: 60.6, standard deviation (SD) 11.5 years) who received initial fornix-based trabeculectomy from a single ophthalmology clinic, with one or more reliable visual field test results per year from at least five years before and after the surgery. Measurements included postoperative mean intraocular pressure (IOP), standard deviation of IOP, medication scores, mean deviation slope, and total deviation slope were evaluated based on preoperative data. The relationship between mean IOP, SD-IOP and the visual field (VF) deterioration speed was also analysed. RESULTS: The mean follow-up period before surgery was 6.15 (SD 0.97) years and post surgery it was 5.95 (SD 0.63) years. The preoperative mean IOP of 14.6 (SD 2.3) mmHg significantly decreased to 9.2 (SD 2.2) mmHg (P <.001). The preoperative medication score 2.7 (SD 0.5) significantly decreased to 0.1 (SD 0.4, P <.001). The preoperative MD slope of -0.52 (SE 0.047) dB/year significantly improved to -0.31 (SE 0.14) dB/year (P <.01), with improvement in the superior hemifield (P ≤.018). Inferior hemifield (P >.10) did not follow the trend. Neither mean IOP nor SD-IOP correlated with the VF deterioration speed. CONCLUSIONS: Fornix-based trabeculectomy is an acceptable procedure for initial surgical management of glaucoma, especially for maintenance of superior VF.

Twelve-month efficacy and safety of glaucoma filtration device for surgery in patients with normal-tension glaucoma.

PURPOSE: To assess the efficacy and safety of filtration surgery using the EX-PRESS glaucoma filtration device in patients with normal-tension glaucoma (NTG). STUDY DESIGN: Prospective, single-arm, multicenter interventional case series. METHODS: Eyes with NTG underwent EX-PRESS implantation with or without cataract surgery. The efficacy and safety were assessed at 1 day; 1 and 2 weeks; and 1, 3, 6, and 12 months after surgery. The main outcome measure was reduction in intraocular pressure (IOP) from baseline at 3, 6, and 12 months after surgery. Safety assessments included adverse event incidence, postoperative inflammation, and corneal endothelial cell density. RESULTS: Thirty-two Japanese patients (37 eyes) with NTG were enrolled. The mean IOP decreased from 14.8 ± 2.3 mmHg at baseline to 10.0 ± 3.1 mmHg at 12 months after surgery (mean reduction 4.9 ± 4.2 mmHg [31.1%]; P < .0001). IOP-lowering medication use decreased from a mean of 3.3 medications per eye before surgery to 0.1 medications per eye at 12 months after surgery. IOP reductions > 20% were achieved by 61.5% of the eyes at 12 months. Adverse events were typical for filtration procedures, and none was deemed device-related. Postoperative inflammation was mild and self-limiting. The mean corneal endothelial cell density had decreased by 3.3% at 12 months after surgery. CONCLUSION: The EX-PRESS glaucoma filtration device is safe and effective for filtration surgery in patients with NTG, providing mean IOP reduction consistent with recommendations based on the Collaborative NTG Study.

Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

Incidence of deepening of the upper eyelid sulcus on treatment with a tafluprost ophthalmic solution.

PURPOSE: Deepening of the upper eyelid sulcus (DUES), one symptom of prostaglandin-associated periorbitopathy, was recently found to be an additional side effect of prostaglandin-related ophthalmic solutions. Here, we prospectively investigated the incidence and factors associated with DUES in Japanese open-angle glaucoma patients initially treated with benzalkonium chloride (BAK)-preserved tafluprost (TAF). METHODS: In this open-label prospective study instilling TAF in one eye, mean deviation (MD) and intraocular pressure (IOP) were measured, and facial photographs and subjective reports of DUES were obtained at intervals over 6 months. Three ophthalmologists independently assessed the photographs of DUES and reached consensus. Relationships between demographic and ocular/systemic factors (age, sex, MD, refraction and IOP reduction) and DUES occurrence were evaluated. RESULTS: Forty-three eyes of 43 glaucoma patients (24 men and 19 women) were evaluated. Mean IOP before treatment was 16.6 ± 2.7 and after treatment, 14.1 ± 2.3 mmHg (P < 0.001). The objective rate of DUES was 9 % (4/43) at 2 months, 14 % (6/43) at 4 months and 14 % (6/43) at 6 months. During this period, only one patient self-reported an occurrence of DUES. No significant association was found between DUES occurrence and any of the demographic, ocular, or systemic factors. CONCLUSIONS: Physicians should inform patients about DUES as a minor side effect when prescribing TAF for IOP control.

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

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

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

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

Recovery from deepening of the upper eyelid sulcus after switching from bimatoprost to latanoprost.

PURPOSE: Although useful for reducing intraocular pressure (IOP), bimatoprost (BIM) can cause deepening of the upper eyelid sulcus (DUES), one of the symptoms of prostaglandin-associated periorbitopathy (PAP). We investigated recovery from BIM-induced DUES after switching treatment to latanoprost (LAT). DESIGN: Prospective, observer-masked, open-label study. METHODS: Twenty-five Japanese patients suffering from primary open-angle glaucoma treated with LAT in both eyes for longer than 6 months and requiring further IOP reduction were prospectively enrolled in the study. During the first 6 months after the switch to BIM, 15 of the 25 patients (60 %) developed DUES. Among these patients, 13 were switched back to LAT and re-examined for DUES at 2-month intervals for an additional 6 months. RESULTS: Two months after the switch back to LAT, for 11 of the 13 patients (85 %) the DUES symptoms had either decreased or disappeared, and this was maintained for at least 6 months. During this time, 6 of 8 patients (75 %) subjectively positive for DUES self-reported a decrease in DUES. CONCLUSIONS: Although DUES is a frequent side effect of treatment with BIM, switching to LAT may reverse the condition for most patients.

Common variants on chromosome 9p21 are associated with normal tension glaucoma.

Although intraocular pressure (IOP) is the most definitive cause of glaucoma, a subtype of open angle glaucoma (OAG) termed normal tension glaucoma (NTG), which occurs in spite of normal IOP, accounts for a large part of glaucoma cases, especially in Japan. To find common genetic variants contributing to NTG in Japanese patients, we conducted a genome-wide association study (GWAS). We performed the first screening for 531,009 autosomal SNPs with a discovery cohort of 286 cases and 557 controls, and then a second screening for the top 30 suggestive loci in an independent cohort of 183 cases and 514 controls. Our findings identified a significantly associated SNP; rs523096 [combined p-value = 7.40× 10(-8), odds ratio (OR)= 2.00 with 95% confidence interval (CI) 1.55-2.58] located 10 kbp upstream of CDKN2B on chromosome 9p21. Moreover, analysis of another independent case-control set successfully replicated the results of the screening studies (combined values of all 3 stages p = 4.96 × 10(-11), OR= 2.13 with 95% CI 1.69-2.68). The SNPs near rs523096 were recently reported to be associated with OAG associated with elevated IOP in primary open-angle glaucoma (POAG), the predominant subtype of glaucoma in Caucasian populations. Our results revealed that the 9p21 locus is also associated with NTG in Japanese. In addition, we identified SNPs more strongly associated with NTG.

Risk factors for progression of normal-tension glaucoma under ß-blocker monotherapy.

PURPOSE: To prospectively study prognostic factors for normal-tension glaucoma (NTG) under treatment with topical ß-blocker. METHODS: One hundred and forty-six eyes of 146 patients with NTG with a mean untreated intraocular pressure (IOP) of 14 mmHg, mild to moderate visual field damage and mean spherical equivalent refraction of -3.5 (-8.0 to +2.0) dioptre were randomized to topical nipradilol or timolol and followed for 3 years. The Humphrey full threshold 30-2 visual field test was performed every 6 months, and optic disc photographs were obtained every 12 months. Progression was defined as visual field progression, optic disc and/or peripapillary nerve fibre layer change, and factors relating to progression were evaluated using Cox proportional hazards models. RESULTS: IOP decreased by 1.0 mmHg over the 3-year period, during which 35% showed progression according to the aforementioned criteria. Optic disc haemorrhage (hazard ratio [HR] 4.00, p < 0.001) and less extent of myopia (per dioptre, HR 1.15, p = 0.013) were significant risk factors. When progression was defined by visual field progression only, less extent of myopia was again a significant risk factor (HR 1.17, p = 0.038). CONCLUSION: Beside optic disc haemorrhage, less extent of myopia was a risk factor for progression in the current NTG population where most patients were mildly myopic and IOP during follow-up averaged 13.2 mmHg under topical ß-blocker.

Incidence of deepening of the upper eyelid sulcus after switching from latanoprost to bimatoprost.

PURPOSE: To investigate the incidence of deepening of the upper eyelid sulcus (DUES) after use of bimatoprost in Japanese glaucoma patients. METHODS: Twenty-five open-angle glaucoma Japanese patients treated with latanoprost in both eyes for 6 months or longer and needing further intraocular pressure (IOP) reduction were enrolled prospectively. Latanoprost was switched to bimatoprost, and the patients were observed at 1, 3, and 6 months. The patients were queried for the presence of DUES at every visit. Sex, refraction, and IOP were evaluated as related factors. The photographs of the eyes and forehead taken at each of the four visits were randomly displayed and judged for the presence of DUES with unanimous confirmation by three examiners. RESULTS: One month after the switch to bimatoprost, 44% (11/25) of the patients had DUES, including three with unilateral DUES. At 3 and 6 months, 60% (15/25) of the patients had DUES. The incidence was significantly higher in older patients and nonmyopic eyes (P < 0.01), but not related to sex or IOP reduction. Finally, 53.3% (8/15) of the patients objectively judged to have DUES noticed the presence of DUES by themselves. Only one patient dropped out of the study because of DUES (after 3 months). CONCLUSION: DUES is an often-observed side effect of bimatoprost topical treatment in Japanese glaucoma patients.