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.

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.

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.

Effect of magnification error and axial length on circumpapillary capillary density and retinal nerve fiber layer thickness.

This study aimed to evaluate the effect of magnification error and axial length (AL) on circumpapillary capillary density (cpCD) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) in healthy eyes. Seventy-two healthy eyes of 72 subjects with AL 24.7 ± 1.5 mm (range: 20.9-28.0 mm) were enrolled in this retrospective cross-sectional study and underwent optical coherence tomography angiography scanning. Magnification corrected measurement areas were obtained using AL upon which corrected cpCD, cpRNFLT values were determined. Relationships between AL and the percentage difference between corrected and uncorrected values (ΔcpCD, ΔcpRNFLT) as well as the effect of AL on magnification corrected cpCD, cpRNFLT were evaluated. ΔcpCD significantly increased with AL in the global, inferior nasal and superior nasal sectors (all p < 0.001). ΔcpRNFLT significantly increased with AL in global and all sectors (all p < 0.001) and the correlations were significantly stronger than that of ΔcpCD-AL in all sectors (all p < 0.001). Corrected cpCD did not associate with AL while corrected cpRNFLT demonstrated a significant positive association with AL in the global (p = 0.005) and temporal sector (p < 0.001). Magnification error led to a significant underestimation of cpCD in eyes with longer AL although its underestimation and the effect of AL was smaller in comparison to that of cpRNFLT.

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.

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.

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.

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.

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.

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.

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.

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.

Human iris pigment epithelium suppresses activation of bystander T cells via TGFbeta-TGFbeta receptor interaction.

Iris pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cultured human iris pigment epithelial (h-IPE) cells that were established from fresh iris tissues can also inhibit the activation of T cells in vitro. We found that cultured h-IPE cells significantly inhibited T cell proliferation and the IFN-gamma production by the target T cells from both the allogeneic and autogeneic peripheral blood mononuclear cells (PBMCs). The h-IPE cells also inhibited the activation of CD4(+) T cells from patients with active uveitis. The suppression by h-IPE occurred in a completely contact-dependent manner. The h-IPE constitutively expressed transforming growth factor beta (TGFbeta) and the receptors, and the T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFbeta2-siRNA transfected h-IPE failed to inhibit activation of responder T cells. Similarly, h-IPE cells in the presence of anti-TGFbeta neutralizing antibodies or recombinant TGFbeta receptor blocking proteins failed to inhibit the T-cell activation. In conclusion, cultured human iris pigment epithelium fully inhibits T cell activation in vitro. Our data support the hypothesis that the ocular resident cells play a critical role in immunosuppression in the eye.

Human iris pigment epithelial cells suppress T-cell activation via direct cell contact.

The purposes of the present study were to investigate whether cultured human iris pigment epithelial (hIPE) cells acquire the ability to modify T-cell activation, and if so, to identify the mechanism. Human IPE cells were prepared from patients who underwent glaucoma surgery, and were cultured in RPMI 1640 medium containing 10% fetal calf serum for 4-7 days. Expression of MHC molecules and co-stimulatory molecules on cultured hIPE cells either unstimulated or stimulated with IFN-gamma was examined by FACS. In addition, peripheral blood T cells were incubated with cultured hIPE cells prepared from the same patients and anti-CD3 antibody in a transwell culture system, or in the presence of anti-PD-L1 and PD-L2 antibodies, and T cell proliferation was assessed by [3H]-thymidine incorporation. The hIPE cells inhibited anti-CD3-driven T-cell activation but the inhibition was diminished when tested in the transwell culture system, indicating that a contact-dependent mechanism is important in the immunoregulatory roles of hIPE. Although cultured hIPE cells expressed Class I and PD-L1 but not Class II or PD-L2, all these molecules were observed on hIPE cells cultured in the presence of IFN-gamma. Blocking antibodies against both PD-L1 and PD-L2 reduced the immunoregulatory activity of hIPE cells. Our data indicates that cultured hIPE cells inhibit T-cell activation by T-cell receptor ligation, which is mediated by cell-to-cell contact in part via the PD-L1 and PD-L2 pathways.

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.

Efficacy and safety of transconjunctival scleral flap resuturing for hypotony after glaucoma filtering surgery.

BACKGROUND: To evaluate the efficacy and safety of transconjunctival scleral flap resuturing for the management of hypotony-associated excess filtration after glaucoma filtering surgery. METHODS: Fifty-six eyes of 55 patients with hypotony maculopathy and/or choroidal detachment caused by excess filtration after glaucoma filtering surgery underwent transconjunctival scleral flap resuturing directly through the conjunctiva, using a 10-0 nylon suture with a round tapered needle. Intraocular pressure (IOP) after suture, best-corrected visual acuity, rate of resolution of hypotony maculopathy and choroidal detachment, rate of complication, and rate of supplemental surgical treatment were assessed. RESULTS: IOP (mean +/- SD) was 2.9 +/- 1.4 mmHg before suture, and elevated significantly to 7.3 +/- 4.5 mmHg at 1 week after suture, 7.2 +/- 3.5 mmHg at 1 month, 8.4 +/- 4.1 mmHg at 1 year, and 8.1 +/- 3.5 mmHg at the last follow-up (mean of 23 months). The best-corrected visual acuity was improved. Hypotony maculopathy was resolved in 92% and choroidal detachment in 100% of the patients. None of the patients required supplemental surgical treatment, because transconjunctival scleral flap resuturing failed to increase IOP. Suture removal was performed in 14 eyes that showed high IOP after suture. Of these eyes, six required needle revision and one required surgical bleb revision. In two eyes, aqueous humor leak after suture was controlled by wearing contact lenses. No bleb-associated infection was observed. CONCLUSION: Even though additional treatments such as repeated suture, suture removal, and needle revison were necessary in some cases, transconjunctival scleral flap resuturing is a simple and minimally invasive procedure that improves hypotony after glaucoma filtering surgery, with no serious complication.

Clinical efficacy of topical nipradilol and timolol on visual field performance in normal-tension glaucoma: a multicenter, randomized, double-masked comparative study.

PURPOSE: To compare the effects of topical nipradilol and timolol on the visual field in Japanese normal-tension glaucoma (NTG) patients. METHODS: We enrolled 146 NTG patients. At baseline, age, intraocular pressure (IOP), and mean deviation (MD) by the Humphrey field analyzer were 47.6 (SD 8.5), 14.2 (1.7) mmHg, and -4.5 (3.0) dB. Seventy-two patients were randomly assigned to the 0.25% nipradilol group and 74 patients to the 0.5% timolol ophthalmic solution group twice daily for the 3-year study period. The Humphrey full-threshold 30-2 visual field test was performed every 6 months. The primary end point was the nonparametric O'Brien summary score (sum of the ranks of six slopes calculated from the average of the total deviation in each cluster) in each patient. The secondary analyses were differences in the MD slope, average of the total deviation in each cluster, the corrected pattern standard deviation (CPSD), and the time course of IOP. RESULTS: No significant intergroup differences were found in baseline characteristics, or in the parameters of the primary and secondary analyses. In both groups, central superior clusters showed negative slopes and IOP decreased by about 1 mmHg from baseline. CONCLUSION: No significant difference in visual field performance or IOP reduction was seen between the nipradilol and timolol groups.

[Tajimi Study review].

The results of The Tajimi Study (a population-based prevalence survey of glaucoma in Tajimi City performed by the Japan Glaucoma Society) are summarized. The Tajimi Study was carried out from September, 2000 to October, 2001 to investigate the prevalence of glaucoma among residents aged 40 years old or over in Tajimi. Seventy-eight point one % of 3,870 eligible people from 4,000 subjects who had been randomly selected from the 54,165 over 40 years old residents in Tajimi participated in the study. Estimated prevalence of all glaucoma and glaucoma/suspected glaucoma were 5.0 (95% confidence interval [CI], 4.2-5.8)% and 7.5 (95% CI, 6.5-8.4)%. The prevalence of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), and secondary glaucoma (SG) were 3.9 (95% CI, 3.2-4.6)%, 0.6 (95% CI, 0.4-0.9)%, and 0.5 (95% CI, 0.2-0.7)%, respectively. Including suspected cases, the prevalence of POAG, PACG, and SG was 6.0 (5.1-6.8)%, 0.8 (0.5-1.2)%, 0.7 (0.4-1.0)%. High intraocular pressure, myopia, and older age were shown to be statistically significant risk factors for POAG. It was suggested that the Frequency Doubling Technology is a good candidate as a screening test for glaucoma. The leading cause of low vision was cataracts. Investigation of refractive status showed that the prevalence of myopia(spherical equivalence [SE] < 0.5 diopters) and high myopia (SE < -5.0 diopters) was 41.8 (40.0-43.6)% and 8.2 (7.2-9.2)%, respectively.

Performance of frequency-doubling technology perimetry in a population-based prevalence survey of glaucoma: the Tajimi study.

OBJECTIVE: To evaluate the performance of frequency-doubling technology (FDT) perimetry in a population-based glaucoma prevalence survey. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Participants older than 40 years randomly selected from the population of Tajimi City. METHODS: Each participant underwent screening ophthalmic examinations including a visual field test using FDT with the C-20-1 screening protocol. A diagnosis of glaucoma was determined by glaucoma specialists with another detailed visual field test using Humphrey Field Analyzer (HFA; Humphrey Instruments, San Leandro, CA) with the 30-2 Swedish interactive threshold algorithm standard protocol and stereoscopic disc photographs. MAIN OUTCOME MEASURES: The ratios of reliable FDT results and the sensitivity and specificity for detecting glaucoma in a general population. RESULTS: Of 5784 eyes of 2892 participants (age range, 40-92 years; refractive error, -23 to 11 diopters) in whom FDT was performed in both eyes, reliable results (< or =33% fixation loss and < or =33% false-positive errors) were obtained in 5707 eyes (98.7%), including 2871 right eyes (99.3%) and 2836 left eyes (98.1%) with a significant bilateral difference (P<0.001, chi-square test). The rate of reliable FDT results did not differ between men and women (P = 0.81) but decreased with age. In 5582 eyes with reliable FDT results, FDT showed 1 or more abnormal points in the visual field in 502 eyes (9.0%), including 388 (7.3%) of 5295 normal eyes, 19 (16.4%) of 116 eyes of glaucoma suspects, and 95 (55.6%) of 171 eyes with definite glaucoma. The sensitivity and specificity values for detecting definite glaucoma were 55.6% and 92.7%, respectively. The positive and negative predictive values were 18.9% and 98.5%, respectively. In further analyses stratified with the mean deviation (MD) of the HFA, the sensitivities were 32.1%, 48.4%, 73.7%, and 96.6% for detecting definite glaucoma with an MD of more than -2 dB, an MD of -2 dB or less and more than -5 dB, an MD of -5 dB or less and more than -8 dB, and an MD of -8 dB or less, respectively. CONCLUSIONS: In a population-based glaucoma screening study, FDT perimetry with the C-20-1 screening protocol was reliably performed in more than 98% of participants. The sensitivity for detecting glaucomatous visual field damages, especially early damage, was not sufficiently high, whereas the specificity was high.