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.

Assessment of Iris Trabecular Contact in Eyes with Gonioscopic Angle-Closure.

PURPOSE: To investigate the extent of iris trabecular contact (ITC) measured by anterior segment OCT (AS-OCT) and its association with primary angle-closure (PAC) and PAC glaucoma (PACG) in eyes with gonioscopic angle-closure and to determine the diagnostic performance of ITC for detection of gonioscopic angle-closure. DESIGN: Multicenter, prospective study. PARTICIPANTS: A total of 119 healthy participants with gonioscopic open-angle and 170 patients with gonioscopic angle-closure (94 with PAC suspect and 76 with PAC/PACG) were included. METHODS: One eye of each subject was randomly selected for AS-OCT imaging. Angle-opening distance (AOD500) and trabecular iris space area (TISA500) were measured every 10° for 360°. Two criteria of ITC500 were examined: (1) AOD500 = 0 mm and (2) TISA500 = 0 mm2. The association between the extent of ITC500 and PAC/PACG in eyes with gonioscopic angle-closure was analyzed with logistic regression analysis. MAIN OUTCOME MEASURES: Sensitivity and specificity of ITC500 for detection of gonioscopic angle-closure; odds ratio (OR) of PAC/PACG. RESULTS: The sensitivity of ITC500 ≥ 10° for detection of gonioscopic angle-closure ranged from 82.4% (AOD500 = 0 mm) to 84.7% (TISA500 = 0 mm2), and the specificity was 85.7% (for both AOD500 = 0 mm and TISA500 = 0 mm2). The extent of ITC500 determined by AS-OCT, not cumulative gonioscopy score (i.e., the sum of the modified Shaffer grades over 4 quadrants), was associated with the odds of PAC/PACG in eyes with gonioscopic angle-closure; the odds of PAC/PACG increased by 5% for every 10° increase in ITC500 (OR, 1.051, 95% confidence interval [CI], 1.022-1.080 for AOD500 = 0 mm; OR, 1.049, 95% CI, 1.022-1.078 for TISA500 = 0 mm2). Axial length and anterior chamber depth were not associated with PAC/PACG in eyes with gonioscopic angle-closure (P ≥ 0.574). CONCLUSIONS: A greater extent of ITC measured by AS-OCT, not angle-closure determined by gonioscopy, was associated with a greater odds of PAC/PACG in eyes with gonioscopic angle-closure.

Synergic effects of EP2 and FP receptors co-activation on Blood-Retinal Barrier and Microglia.

Macular edema (ME) is caused with disruption of the blood-retinal barrier (BRB) followed by fluid accumulation in the subretinal space. Main components of the outer and inner BRB are retinal pigment epithelial (RPE) cells and retinal microvascular endothelial cells, respectively. In addition, glial cells also participate in the functional regulation of the BRB as the member of 'neurovascular unit'. Under various stresses, cells in neurovascular units secrete inflammatory cytokines. Neuroinflammation induced by these cytokines can cause BRB dysfunction by degrading barrier-related proteins and contribute to the pathophysiology of ME. Prostaglandins (PGs) are crucial lipid mediators involved in neuroinflammation. Among PGs, a novel EP2 agonist, omidenepag (OMD) acts on not only the uveoscleral pathway but also the conventional pathway, unlike F prostanoid (FP) receptor agonists. Moreover, the combination use of the EP and the FP agonist is not recommended because of the risk of inflammation. In this study, we investigated effects of OMD and latanoprost acid (LTA), a FP agonist, on BRB and microglia in vitro and in vivo. To investigate the function of outer/inner BRB and microglia, in vitro, ARPE-19 cells, human retinal microvascular endothelial cells (HRMECs), and MG5 cells were used. Cell viability, inflammatory cytokines mRNA and protein levels, barrier morphology/function, and microglial activation were evaluated using proliferation assays, qRT-PCR, ELISA, immunocytochemistry, trans-epithelial electrical resistance, and permeability assay. Moreover, after vitreous injection into the mouse, outer BRB morphology, glial activation, and cytokine expression were assessed. Each OMD and LTA alone did not affect the viability or cytokines expression of the three types of cells. In ARPE-19 cells, the co-stimulation of OMD and LTA increased the mRNA and protein levels of inflammatory cytokines (IL-6, TNF-α, and VEGF-A) and decreased the barrier function and the junction-related protein (ZO-1 and ß-catenin). By contrast in HRMECs, the co-stimulation affected significant differences in the mRNA levels of some cytokine (IL-6 and TNF-α) but enhanced the barrier function. In MG5 cells, the cytokines mRNA and size of Iba1-expressed cell were increased. A non-steroidal anti-inflammatory inhibited the barrier dysfunction and the junction-related protein downregulation in ARPE-19 cells and activation of MG5 cells. Also in vivo, the co-stimulation induced outer BRB disruption, cytokine increase, and retinal glial activation. Therefore, the co-stimulation of EP2 and FP induced the inflammatory cytokine-mediated outer BRB disruption, the enhanced inner BRB function, and the microglial activation. The BRB imbalance and the intrinsic prostaglandin production may be involved in OMD-related inflammation.

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.

Factors Associated with Progression of Japanese Open-Angle Glaucoma with Lower Normal Intraocular Pressure.

PURPOSE: To characterize the natural history and define the risk factors associated with the progression of normal-tension glaucoma (NTG) in Japanese patients who were followed up closely without treatment. DESIGN: Prospective 5-year study. PARTICIPANTS: Patients with NTG with intraocular pressure (IOP) consistently ≤15 mmHg without treatment at baseline. METHODS: Visual field (VF) examinations were performed every 3 months, and disc/peripapillary retina photographs were taken every 6 months. Patients were followed up without treatment. MAIN OUTCOME MEASURES: Deterioration in VF was defined by reference to Guided Progression Analysis Software of the Humphrey VF Swedish Interactive Thresholding Algorithm 24-2 (Carl Zeiss Meditec, Jena, Germany) and disc/peripapillary retina deterioration as adjudged by 3 independent observers. Life table analysis was used for evaluating the time to disease progression, as defined by VF or deterioration of the optic nerve head structure. The Cox proportional hazards model was used to identify risk factors for glaucoma progression. RESULTS: We enrolled 90 patients (mean age, 53.9 years; baseline IOP, 12.3 mmHg; mean deviation [MD], -2.8 decibels [dB]). The MD slope averaged -0.33 dB/year (median, -0.23; 95% confidence interval [CI], -0.44 to -0.22). Glaucoma progression probability at 5 years was 66% (95% CI, 55-78), as defined by VF deterioration or disc/peripapillary retina deterioration (criterion 1): 52% (95% CI, 37-60), as defined by VF deterioration (criterion 2), and 50% (95% CI, 38-71), as defined by disc/peripapillary retina deterioration (criterion 3). Presence or history of disc hemorrhage (DH) (P < 0.001), long-term IOP fluctuation (P = 0.020), and a greater vertical cup-to-disc ratio (v-C/D) (P = 0.018) were significant predictors for progression defined by criterion 1. Long-term IOP fluctuation (P = 0.011) and a greater v-C/D (P = 0.036) were significant predictors for progression by criterion 2. Presence or history of DH (P = 0.0018) and long-term IOP fluctuation (P = 0.022) were significant predictors for progression by criterion 3. CONCLUSIONS: In Japanese patients with NTG with mean baseline IOP of 12.3 mmHg without treatment, estimated mean MD slope for 5 years was -0.33 dB/year; probability of glaucoma progression based on VF or disc/peripapillary end points at 5 years was 66%. Presence or history of DH, long-term IOP fluctuation, and greater v-C/D significantly contributed to progression.

Visual acuity improvement after phacoemulsification cataract surgery in patients aged ≥90 years.

BACKGROUND: Visual acuity (VA) outcomes after phacoemulsification cataract surgery in the very elderly (≥90 years) compared to those in younger patients remain unclear till date. METHODS: We retrospectively investigated 138 (group 1) and 152 (group 2) eyes in patients aged ≥90 and < 80 years, respectively, with senile cataracts who underwent phacoemulsification and intraocular lens implantation between 2014 and 2016. Four highly experienced ophthalmic surgeons performed the procedures. Intra- and post-operative complications were compared between the two groups. To investigate the effectiveness of cataract surgery in improving best-corrected VA (BCVA) at 1 and 3 months postoperatively, multiple regression analysis was performed with variables of age, cataract grades, sex, and history of diabetes mellitus (DM) and hypertension. RESULTS: The intra- and post-operative complication rates were similar between the two groups. After adjusting for the difference in cataract grades, multiple regression analysis indicated that BCVA improvement was equally favorable in both groups at 1 and 3 months postoperatively but was less favorable in patients with a history of DM at 3 months postoperatively (P = 0.042). CONCLUSION: Phacoemulsification in patients aged ≥90 years improves VA as effectively and safely as it does in younger patients, at least when performed by experienced surgeons.

[Foreign Body in the Anterior Chamber 10 Months after Uneventful Cataract Surgery].

PURPOSE: A foreign body detected in the anterior chamber 10 months after uneventful sutureless cataract surgery. CASE REPORT: Clear corneal phacoemulsification and intraocular lens placement (PEA + IOL) were performed on a 74-year-old man suffering from vision loss caused by senile cataracts. After uneventful surgery, the postoperative course appeared to be problem-free. OBSERVATION: However, 10 months after the operation, the patient reported blurred vision. Slit-lamp examination revealed an oil droplet, reminiscent of a foreign body, about 1 mm in diameter, on the IOL surface. The visual acuity problem did not become exacerbated and the anterior segment of the eye remained intact. Although we removed the foreign body, qualitative testing was impossible because the body disintegrated. CONCLUSIONS: A rare case of a foreign body in the anterior chamber 10 months after uneventful PEA + IOL. We are of the view that the body may have been composed of ophthalmic ointment delivered from the conjunctival sac at the end of surgery.

Factors associated with visual field or structure progression occurring first in a prospective study on patients with untreated open-angle glaucoma with normal intraocular pressure.

BACKGROUND/OBJECTIVES: To identify factors associated with disc/retina deterioration in stereo fundus photographs preceding that of the visual field (VF), as determined with a Humphrey Field Analyzer (HFA) (Structure First deterioration) and factors associated with the latter preceding the former (Field First deterioration) in open-angle glaucoma (OAG) with lower normal intraocular pressure (IOP). SUBJECTS/METHODS: Prospective cohort study. Ninety eyes of 90 patients with OAG and a baseline IOP < 15 mmHg participated in a 5-year prospective study without treatment. IOP measurements and HFA 24-2 Swedish Interactive Test Algorithm Standard tests were performed every 3 months, and fundus photographs were obtained every 6 months. VF deterioration was determined by Guided Progression Analysis and deterioration of disc/retina was determined on stereophotographs by an independent committee. A multivariable Cox proportional hazard model was used to identify factors associated with Structure First deterioration, and with Field First deterioration. RESULTS: The average baseline age and mean deviation were 53.9 ± 9.8 years and -2.8 ± 2.8 dB, respectively. During the 5-year follow-up, the probability of Field First deterioration was 49% ± 6.6% (standard error) and that of Structure First deterioration was 33% ± 6.4% (P = 0.062, log-rank test). Disc hemorrhage (DH) prior to the event (P = 0.006) was associated with Structure First deterioration, and older age was associated with Field First deterioration (P = 0.040). CONCLUSIONS: In OAG eyes with lower normal IOP, DH was significantly associated with Structure First deterioration, and age was significantly associated with Field First deterioration.

Cost-effectiveness analysis of prophylactic laser peripheral iridotomy for primary angle-closure suspect in Japan.

BACKGROUND/OBJECTIVES: This study aimed to compare the cost-effectiveness of prophylactic laser peripheral iridotomy (LPI) with that of observation for primary angle-closure suspect (PACS) in Japan. SUBJECTS/METHODS: A Markov model was developed to compare the costs and utilities of prophylactic LPI with those of observation of 40-year-old patients with PACS. In the model with a yearly cycle over a 20-year time horizon, the disease was postulated to irreversibly progress from PACS to primary angle closure, followed by primary angle-closure glaucoma, unilateral blindness, and bilateral blindness. The parameters were estimated mainly based on a recent randomised controlled trial and analyses of Japanese claims data. The incremental cost-effectiveness ratio was estimated from the healthcare payer's perspective and evaluated at the willingness-to-pay 5 million Japanese Yen per quality-adjusted life-year. The observation period and the age at entry into the cohort was changed to account for a variety of clinical courses in sensitivity analyses. We conducted one-way deterministic sensitivity analysis and probabilistic sensitivity analysis with Monte Carlo simulations with 10 000 iterations. RESULTS: The incremental cost-effectiveness ratio of LPI was 2,287,662 Japanese Yen (14,298 pounds sterling) per quality-adjusted life-year, which was below the willingness-to-pay threshold. The ratios were approximately 4 and 8 million in the 15-year and 10-year time horizons, respectively. Increasing the age at entry had little influence on the incremental cost-effectiveness ratio. The deterministic and probabilistic sensitivity analyses indicated that the results were robust. CONCLUSIONS: Our results indicate that prophylactic LPI for middle-aged patients with PACS is cost-effective in Japan.

Neuroprotective effect of omidenepag on excitotoxic retinal ganglion cell death regulating COX-2-EP2-cAMP-PKA/Epac pathway via Neuron-Glia interaction.

Glutamate excitotoxicity is involved in retinal ganglion cell (RGC) death in various retinal degenerative diseases, including ischemia-reperfusion injury and glaucoma. Excitotoxic RGC death is caused by both direct damage to RGCs and indirect damage through neuroinflammation of retinal glial cells. Omidenepag (OMD), a novel E prostanoid receptor 2 (EP2) agonist, is a recently approved intraocular pressure-lowering drug. The second messenger of EP2 is cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). In this study, we investigated the neuroprotective effects of OMD on excitotoxic RGC death by focusing on differences in cAMP downstream signaling from the perspective of glia-neuron interactions. We established a glutamate excitotoxicity model in vitro and NMDA intravitreal injection model in vivo. In vitro, rat primary RGCs were used in an RGC survival rate assay. MG5 cells (mouse microglial cell line) and A1 cells (astrocyte cell line) were used for immunocytochemistry and Western blotting to evaluate the expressions of COX-1/2, PKA, Epac1/2, pCREB, cleaved caspase-3, inflammatory cytokines, and neurotrophic factors. Mouse retinal specimens underwent hematoxylin and eosin staining, flat-mounted retina examination, and immunohistochemistry. OMD significantly suppressed excitotoxic RGC death, cleaved caspase-3 expression, and activated glia both in vitro and in vivo. Moreover, it inhibited Epac1 and inflammatory cytokine expression and promoted COX-2, pCREB, and neurotrophic factor expression. OMD may have neuroprotective effects through inhibition of the Epac pathway and promotion of the COX-2-EP2-cAMP-PKA pathway by modulating glia-neuron interaction.

Diagnostic criteria of anterior segment swept-source optical coherence tomography to detect gonioscopic angle closure.

AIMS: To compare the diagnostic performance of 360° anterior segment optical coherence tomography assessment by applying normative percentile cut-offs versus iris trabecular contact (ITC) for detecting gonioscopic angle closure. METHODS: In this multicentre study, 394 healthy individuals were included in the normative dataset to derive the age-specific and angle location-specific normative percentiles of angle open distance (AOD500) and trabecular iris space area (TISA500) which were measured every 10° for 360°. 119 healthy participants and 170 patients with angle closure by gonioscopy were included in the test dataset to investigate the diagnostic performance of three sets of criteria for detection of gonioscopic angle closure: (1) the 10th and (2) the 5th percentiles of AOD500/TISA500, and (3) ITC (ie, AOD500/TISA500=0 mm/mm2). The number of angle locations with angle closure defined by each set of the criteria for each eye was used to generate the receiver operating characteristic (ROC) curve for the discrimination between gonioscopic angle closure and open angle. RESULTS: Of the three sets of diagnostic criteria examined, the area under the ROC curve was greatest for the 10th percentile of AOD500 (0.933), whereas the ITC criterion AOD500=0 mm showed the smallest area under the ROC (0.852) and the difference was statistically significant with or without adjusting for age and axial length (p<0.001). The criterion ≥90° of AOD500 below the 10th percentile attained the best sensitivity 87.6% and specificity 84.9% combination for detecting gonioscopic angle closure. CONCLUSIONS: Applying the normative percentiles of angle measurements yielded a higher diagnostic performance than ITC for detecting angle closure on gonioscopy.

Crystalline lens nuclear age prediction as a new biomarker of nucleus degeneration.

BACKGROUND: The crystalline lens is a transparent structure of the eye to focus light on the retina. It becomes muddy, hard and dense with increasing age, which makes the crystalline lens gradually lose its function. We aim to develop a nuclear age predictor to reflect the degeneration of the crystalline lens nucleus. METHODS: First we trained and internally validated the nuclear age predictor with a deep-learning algorithm, using 12 904 anterior segment optical coherence tomography (AS-OCT) images from four diverse Asian and American cohorts: Zhongshan Ophthalmic Center with Machine0 (ZOM0), Tomey Corporation (TOMEY), University of California San Francisco and the Chinese University of Hong Kong. External testing was done on three independent datasets: Tokyo University (TU), ZOM1 and Shenzhen People's Hospital (SPH). We also demonstrate the possibility of detecting nuclear cataracts (NCs) from the nuclear age gap. FINDINGS: In the internal validation dataset, the nuclear age could be predicted with a mean absolute error (MAE) of 2.570 years (95% CI 1.886 to 2.863). Across the three external testing datasets, the algorithm achieved MAEs of 4.261 years (95% CI 3.391 to 5.094) in TU, 3.920 years (95% CI 3.332 to 4.637) in ZOM1-NonCata and 4.380 years (95% CI 3.730 to 5.061) in SPH-NonCata. The MAEs for NC eyes were 8.490 years (95% CI 7.219 to 9.766) in ZOM1-NC and 9.998 years (95% CI 5.673 to 14.642) in SPH-NC. The nuclear age gap outperformed both ophthalmologists in detecting NCs, with areas under the receiver operating characteristic curves of 0.853 years (95% CI 0.787 to 0.917) in ZOM1 and 0.909 years (95% CI 0.828 to 0.978) in SPH. INTERPRETATION: The nuclear age predictor shows good performance, validating the feasibility of using AS-OCT images as an effective screening tool for nucleus degeneration. Our work also demonstrates the potential use of the nuclear age gap to detect NCs.

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.

One-year costs of incisional glaucoma surgery and laser therapy.

BACKGROUND: This study aimed to calculate one-year total costs of incisional glaucoma surgery and laser therapy in a real-world clinical setting. METHODS: We conducted a retrospective cohort study from July 2010 to March 2021 using the Diagnosis Procedure Combination database. We included patients hospitalized for incisional glaucoma surgery (trabeculectomy, trabeculotomy, tube shunt surgery, Ex-PRESS surgery, or iStent implantation) or laser therapy (laser peripheral iridotomy, surgical iridectomy, laser trabeculoplasty, cyclocryotherapy, or cyclophotocoagulation). The outcomes were total costs, including costs of hospitalization, re-admissions, antiglaucoma drugs, ophthalmic examinations, and outpatient visits for incisional glaucoma surgery and laser therapy within one year. RESULTS: We identified 49,202 eligible hospitalizations. The one-year median total cost was 707,497 yen [interquartile range: 546,887-944,664 yen]. The median total cost was the highest in patients undergoing tube shunt surgery, followed by Ex-PRESS surgery, iStent implantation, and trabeculectomy. The number and cost of postoperative outpatient visits and length of hospital stay were higher in patients who underwent trabeculectomy and Ex-PRESS surgery than in those after tube shunt surgery. The total costs of laser therapies were lower than those of incisional glaucoma surgeries. The total cost was the highest in the 0-19 age group (856,398 [649,419-1,258,844] yen). CONCLUSIONS: Tube shunt surgery was the costliest in terms of total one-year costs. Trabeculectomy and Ex-PRESS surgery were associated with long hospital stays and incurred high postoperative costs. The costs of laser therapies were relatively low. However, cost-effectiveness of laser therapies compared with incisional surgeries needs to be analyzed in future research.

Differences in Factors Associated With Glaucoma Progression With Lower Normal Intraocular Pressure in Superior and Inferior Halves of the Optic Nerve Head.

Purpose: The purpose of this study was to investigate risk factors for progression in the superior and inferior hemi-visual fields (hemi-VFs) and the corresponding hemi-disc/retinas in eyes with normal tension glaucoma (NTG). Methods: A 5-year prospective follow-up of 90 patients with NTG with untreated intraocular pressure (IOP) consistently ≤ 15 mm Hg was conducted. The IOP and Humphrey Perimeter measurements and disc/retina stereo-photographs were taken every 3 and 6 months, respectively. Risk factors for progression in the superior and inferior hemi-VFs and in the superior and inferior hemi-disc/retinas were investigated. Results: The mean total deviation values decreased at -0.50 ± 0.76 and -0.13 ± 0.34 dB/year in the superior and inferior hemi-VFs, respectively (P < 0.001). In the superior hemi-VF, the risk factor for faster progression was greater long-term IOP fluctuation (P = 0.022). In the inferior hemi-VF, the risk factors were disc hemorrhage (DH), greater myopic refraction, body mass index (BMI), and vertical cup-to-disc ratio (v-C/D; P < 0.05). The progression probability was 47.7 ± 6.0 and 17.7 ± 4.7% at 5 years in the superior and inferior hemi-disc/retinas respectively (P < 0.001), and DH was a risk factor for progression in both (P = 0.001). Conclusions: In NTG eyes, greater BMI, myopia, and v-C/D are characteristic risk factors for faster progression in the superior half of the optic nerve head (ONH), whereas long-term IOP fluctuation is the significant risk factor in the inferior half of the ONH, whereas DH is a risk factor in both. Translational Relevance: Different risk factors were identified in superior and inferior hemifields in NTG eyes.

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.

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.

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.

Reproducibility of deep learning based scleral spur localisation and anterior chamber angle measurements from anterior segment optical coherence tomography images.

AIMS: To apply a deep learning model for automatic localisation of the scleral spur (SS) in anterior segment optical coherence tomography (AS-OCT) images and compare the reproducibility of anterior chamber angle (ACA) width between deep learning located SS (DLLSS) and manually plotted SS (MPSS). METHODS: In this multicentre, cross-sectional study, a test dataset comprising 5166 AS-OCT images from 287 eyes (116 healthy eyes with open angles and 171 eyes with primary angle-closure disease (PACD)) of 287 subjects were recruited from four ophthalmology clinics. Each eye was imaged twice by a swept-source AS-OCT (CASIA2, Tomey, Nagoya, Japan) in the same visit and one eye of each patient was randomly selected for measurements of ACA. The agreement between DLLSS and MPSS was assessed using the Euclidean distance (ED). The angle opening distance (AOD) of 750 µm (AOD750) and trabecular-iris space area (TISA) of 750 µm (TISA750) were calculated using the CASIA2 embedded software. The repeatability of ACA width was measured. RESULTS: The mean age was 60.8±12.3 years (range: 30-85 years) for the normal group and 63.4±10.6 years (range: 40-91 years) for the PACD group. The mean difference in ED for SS localisation between DLLSS and MPSS was 66.50±20.54 µm and 84.78±28.33 µm for the normal group and the PACD group, respectively. The span of 95% limits of agreement between DLLSS and MPSS was 0.064 mm for AOD750 and 0.034 mm2 for TISA750. The respective repeatability coefficients of AOD750 and TISA750 were 0.049 mm and 0.026 mm2 for DLLSS, and 0.058 mm and 0.030 mm2 for MPSS. CONCLUSION: DLLSS achieved comparable repeatability compared with MPSS for measurement of ACA.

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.