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Objective Accurate identification of iridocorneal structures on gonioscopy is difficult to master and errors can lead to grave surgical complications. This study aimed to develop and train convolutional neural networks (CNNs) to accurately identify the trabecular meshwork (TM) in gonioscopic videos in real-time for eventual clinical integrations. Design Cross-sectional study Subjects, Participants, and/or Controls Adult patients with open angle were identified in academic glaucoma clinics in both Taipei, Taiwan and Irvine, California, USA. Methods Neural Encoder-Decoder CNNs (U-nets) were trained to predict a curve marking the TM using an expert-annotated data set of 378 gonioscopy images. The model was trained and evaluated with stratified cross-validation – grouped by patients to ensure uncorrelated training and testing sets, as well as on a separate test set and three intraoperative gonioscopic videos of ab interno trabeculotomy with Trabectome (totaling 90 seconds long, 30 frames per second). We also evaluated our model’s performance by comparing its accuracy against ophthalmologists. Main Outcome Measures Successful development of real-time capable CNNs that are accurate in predicting and marking the trabecular meshwork’s position in video frames of gonioscopic views. Models were evaluated in comparison to human expert annotations of static images and video data. Results The best CNN model produced test set predictions with a median deviation of 0.8% of the video frame’s height (15.25 microns) from the human experts’ annotations. This error is less than the average vertical height of the TM. The worst test frame prediction of this model had an average deviation of 4% of the frame height (76.28 microns), which is still considered a successful prediction. When challenged with unseen images, the CNN model scored greater than two standard deviations above the mean performance of the surveyed general ophthalmologists. Conclusion Our CNN model can identify the TM in gonioscopy videos in real time with remarkable accuracy, allowing it to be used in connection with a video camera intraoperatively. This model can have applications in surgical training, automated screenings, and intraoperative guidance. The dataset developed in this study is the first publicly available gonioscopy image bank which may encourage future investigations in this topic.

Erythropoietin (EPO) is a circulating hormone conventionally considered to be responsible for erythropoiesis. In addition to facilitating red blood cell production, EPO has pluripotent potential, such as for cognition improvement, neurogenesis, and anti-fibrotic, anti-apoptotic, anti-oxidative, and anti-inflammatory effects. In human retinal tissues, EPO receptors (EPORs) are expressed in the photoreceptor cells, retinal pigment epithelium, and retinal ganglion cell layer. Studies have suggested its potential therapeutic effects in many neurodegenerative diseases, including glaucoma. In this review, we discuss the correlation between glaucoma and EPO, physiology and potential neuroprotective function of the EPO/EPOR system, and latest evidence for the treatment of glaucoma with EPO.

Introduction: Current medical therapy for glaucoma consists of topical agents that lower intraocular pressure (IOP). Prostaglandin F2α analogues, the most commonly used class of IOP-lowering drugs,...

Glaucoma can cause irreversible vision loss and is the second leading cause of blindness worldwide. The disease mechanism is complex and various factors have been implicated in its pathogenesis, including ischemia, excessive oxidative stress, neurotropic factor deprivation, and neuron excitotoxicity. Erythropoietin (EPO) is a hormone that induces erythropoiesis in response to hypoxia. However, studies have shown that EPO also has neuroprotective effects and may be useful for rescuing apoptotic retinal ganglion cells in glaucoma. This article explores the relationship between EPO and glaucoma and summarizes preclinical experiments that have used EPO to treat glaucoma, with an aim to provide a different perspective from the current view that glaucoma is incurable.

Background: Encapsulation after Ahmed glaucoma valve (AGV) is difficult to manage and sometimes results in treatment failure. We proposed a novel conjunctival revision method to improve intraocular pressure (IOP) control due to encapsulation after AGV implantation. The efficacy and safety of this method in refractory glaucoma patients were evaluated. Methods: The present study was done in a clinical trial design. Patients of encapsulation after AGV implantation for at least 6 months were enrolled and divided into three groups (control group, single revision group, and repeated revision group). Characteristics such as visual acuity, glaucoma type, IOP change, underlying diabetes mellitus, and complications were assessed. Results: In total, 120 patients were enrolled in this study, and they were randomly divided into three groups on a 1:1:1 base. At the study end, there were 28 patients in the control group, 32 patients in single revision group and 37 patients in repeated revision group. The results showed that the conjunctival revision method significantly reduced the mean IOP of the encapsulated eyes on day 1 after the procedure (24.5 ± 6.3 to 11.8 ± 3.4 mmHg in single revision group and 25.1 ± 4.7 to 10.2 ± 2.3 mmHg in repeated revision group, respectively). The eye pressure was remained relatively low during follow-up visits for 4.17 ± 4.2 months in single revision group, whereas stable IOP could be maintained in repeated revision group for 10.43 ± 3.7 months in average. Changes in preoperative and postoperative visual acuities and the refraction errors were insignificant. Only mild complications occurred and most resolved without treatment. Conclusions: The conjunctival revision could relieve entrapped subconjunctival aqueous and therefore reduced IOP temporarily with single procedure, and IOP could be maintained with repeated procedures. This method is suggested to be a safe and simple alternative for refractory glaucoma patients developed encapsulation after AGV implantation.

Ningli Wang,1 Da-Wen Lu,2 Yingzi Pan,3 Yury Astakhov,4 Tatyana Iureva,5 Adeniyi Adewale,6 Thomas M Walker6 1Beijing Tongren Eye Center, Beijing, People’s Republic of China; 2Tri-Service General Hospital, Taipei, Taiwan; 3Peking University First Hospital, Beijing, People’s Republic of China; 4Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia; 5Irkutsk Branch of the Academician S.N. Fyodorov Eye Microsurgery Federal State Institution, Irkutsk, Russia; 6Novartis Pharmaceuticals Corporation, Fort Worth, TX, USACorrespondence: Ningli WangBeijing Tongren Eye Center, No. 1 Dongjiaomin Str., Dongcheng District, Beijing 100041, People’s Republic of ChinaTel +861058265922Email wningli@vip.163.comObjective: To demonstrate that the intraocular pressure (IOP)-lowering efficacy of a twice-daily brinzolamide 10 mg/mL (BRINZ)/brimonidine 2 mg/mL (BRIM) fixed-dose combination (BBFC) was non-inferior to its individual components (BRINZ+BRIM) dosed concomitantly in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Safety was also evaluated.Methods and Analysis: This was a Phase III, multicenter, observer-masked study in patients from China, Russia and Taiwan. Patients aged ≥ 18 years with a mean IOP ≥ 21 mmHg and ≤ 36 mmHg in the same eye after washout of other IOP-lowering medications were included. Eligible patients were randomized (1:1) to receive BBFC or BRIZ+BRIM eye drops twice daily for 3 months. The primary endpoint was the mean change in diurnal IOP (averaged over 09:00, +2 h, and +7 h) from baseline to Month 3. Adverse events (AEs) were recorded throughout the study.Results: The per-protocol set included 349 patients (BBFC, n=172; BRINZ+BRIM, n=177). The mean±standard deviation diurnal IOP at baseline was 24.6± 2.66 mmHg in both groups. At Month 3, the least square mean±standard error change in diurnal IOP from baseline was − 7.2± 0.34 mmHg and − 7.3± 0.34 mmHg with BBFC and BRINZ+BRIM, respectively (between-group difference: 0.1 mmHg [95% CI − 0.5, 0.7]). In the BBFC and BRINZ+BRIM groups, 53.3% and 55.0% of patients achieved a diurnal IOP < 18 mmHg, and 43.2% and 37.4% of patients, respectively, achieved a mean diurnal IOP reduction > 30% from baseline at Month 3. Ocular AEs were reported in 28.7% (BBFC) and 22.5% (BRINZ+BRIM) of patients; conjunctival hyperemia was the most frequent ocular AE (BBFC, 6.4%; BRINZ+BRIM, 6.8%). Non-ocular AEs were reported in 32.4% (BBFC) and 30.4% (BRINZ+BRIM) of patients.Conclusion: The study findings demonstrate that the efficacy of twice-daily BBFC was non-inferior to BRINZ+BRIM in patients with OAG/OHT. The safety profile of BBFC was similar to that of BRINZ+BRIM.Keywords: brinzolamide/brimonidine fixed-dose combination, intraocular pressure reduction, ocular hypertension, open-angle glaucoma

Introduction Maximal medical therapy (MMT) is the use of ≥3 classes of topical anti-glaucoma agents to achieve maximal intraocular pressure (IOP) reduction while minimizing adverse effects and compliance challenges. Purpose To evaluate the additive IOP-lowering effect of twice-daily brinzolamide 1%/brimonidine 0.2% fixed-dose combination (BBFC) used adjunctively with once daily travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG)/ocular hypertension (OHT). Methods In this phase IV, double-masked study, patients on TTFC for ≥28 days, aged ≥18 years, with mean IOP ≥19 and ≤28 mmHg in at least 1 eye were randomized to receive BBFC+TTFC (n=67) or vehicle+TTFC (n=67) for 6 weeks. The primary endpoint was mean change in diurnal IOP from baseline (BL, averaged over 09:00 and 11:00) at Week 6. Results The study was terminated prematurely due to recruitment challenges. BL mean IOP was similar in both groups (BBFC+TTFC: 21.6±1.78 mmHg; vehicle+TTFC: 21.8±1.90 mmHg). Mean change in diurnal IOP from BL at Week 6 was greater with BBFC+TTFC (-4.25 mmHg, 95% confidence interval [CI]: -4.7, -3.8) than with vehicle+TTFC (-2.11 mmHg, 95% CI: -2.6, -1.6, treatment difference, -2.15 mmHg (95% CI: -2.8, -1.5; P

Background and Objectives: This study introduces a novel office-based procedure involving air–blood exchange under a slit-lamp microscope for treatment of severe hyphema after filtering surgery. Materials and Methods: This retrospective study enrolled 17 patients (17 eyes) with a diagnosis of primary open-angle glaucoma with severe hyphema (≥4-mm height) after filtering surgery. All patients were treated with air–blood exchange under a slit-lamp using room air (12 patients) or 12% perfluoropropane (C3F8, five patients). Results: The procedures were successful in all 17 patients, they exhibited clear visual axes without complications during follow-up. In the room air group, the mean visual acuity (VA) and hyphema height significantly improved from 1.70 ± 1.07 LogMAR and 5.75 ± 1.14 mm before the procedure to 0.67 ± 0.18 LogMAR and 2.83 ± 0.54 mm after the procedure (p = 0.004, p &lt, 0.001). In the C3F8 group, the mean VA showed a trend, though not significant, for improvement from 1.70 ± 1.10 LogMAR to 0.70 ± 0.19 LogMAR (p = 0.08), the mean hyphema height showed a trend for improvement from 5.40 ± 0.96 mm to 3.30 ± 0.45 mm. Compared with the C3F8 group, the room air group showed the same efficacy with a shorter VA recovery time. Conclusions: “Air–blood exchange under a slit-lamp using room air” is a convenient, rapid, inexpensive, and effective treatment option for severe hyphema after filtering surgery, and may reduce the risk of failure of filtering surgery.

For chronic angle-closure glaucoma (ACG), Ahmed glaucoma valve (AGV) is a useful drainage device for intraocular pressure (IOP) control but there are few reports discussing the outcomes of small size AGV in adult patients. This retrospective study involved 43 Asian adult patients (43 eyes) with chronic ACG. All patients had undergone small size AGV insertion and were divided into anterior chamber (AC) group and posterior chamber (PC) group. In the AC group, tube was inserted through sclerectomy gap into the anterior chamber. In the PC group, tube was inserted into posterior chamber through a needling tract. Outcome measures were intraocular pressure (IOP), visual acuity, number of antiglaucoma medications, survival curve and incidence of complications. In total, 43 eyes of 43 patients, 24 in the AC group and 19 in the PC group, were reviewed. The mean follow-up period was 28.5 months (95% confidence interval: 25.5–31.4). Mean IOP had significantly decreased following AGV insertion. The Kaplan–Meier survival analysis demonstrated a probability of success at 24 months of 67.4% for qualified success and 39.5% for complete success. There were no significant differences between the AC and PC groups in terms of the mean IOP, cumulative probability of success, visual acuity change or antiglaucoma medication change, except IOP at 1-day and 1-month mean IOP. The most common complications noted was hyphema in the PC group. For adult chronic ACG patients, small size AGV insertion could be effective at lowering IOP. Besides, tube insertion into AC with sclerectomy may prevent the hypertensive phase in the early postoperative period.

Prcis Acetate dialysate causes elevation of intradialytic intraocular pressure (IOP) and contributed to the rise of IOP in the early years of hemodialysis. Glaucoma, narrow-angle, or impaired aqueous outflow is another moderator causing a rise of intradialytic IOP. Purpose Severe intraocular pressure (IOP) elevation during hemodialysis (HD) has been described in many case reports. However, the results of primary studies are conflicting. This meta-analysis examined the impact of HD on IOP and explored the potential moderators. Methods Medline, PubMed, Embase, Web of Science, and Cochrane were systematically searched. Before-after studies reporting the change of IOP during HD were included. Intradialytic IOP changes were calculated based on four different definitions: highest-baseline, lowest-baseline, max-baseline, and end-baseline IOP difference. Standardized mean difference (SMD) was pooled using the random-effects model. Results 53 studies involving 1903 participants and 2845 eyes were included. Overall data pooling showed no significant rise in intradialytic IOP. However, subgroup analysis showed an intradialytic IOP rise before 1986 (SMD 0.593; 95% CI 0.169 to1.018; max-baseline IOP difference as representative; most studies using acetate dialysate), no change between 1986 and 2005 (using both acetate and bicarbonate), and a decline after 2005 (SMD -0.222; 95% CI -0.385 to -0.063; entirely using bicarbonate). Multivariable meta-regression showed only the type of dialysate, but not publication year or other potential factors, as a significant moderator. Glaucoma was found to be another significant moderator independent of the dialysate effect in bivariate meta-regression. Conclusions IOP rose in the early years of HD due to the effect of acetate dialysate, but this phenomenon is no longer a clinical problem since the substitution of acetate with bicarbonate dialysate. However, physicians should still be cautious of potential IOP changes in the HD population with glaucoma.

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/βcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.

This study aimed to study the long-term surgical outcomes of combined trabeculotomy–trabeculectomy (CTT) using the modified Safer Surgery System in treating childhood glaucoma at a tertiary medical center in Taiwan. Retrospective, consecutive, noncomparative case series. We retrospectively reviewed medical records of 42 pediatric patients (age 0–18 years) who had CTT performed on their 65 eyes using the modified Safer Surgery System. The study period spanned 18 years (from January 1, 1997, to December 31, 2014). We evaluated the outcome in terms of postoperative intraocular pressure (IOP), axial length growth, disc cupping reversal, and use of antiglaucoma medications. The surgical success was rated using the Kaplan–Meier survival analysis and based on the incidence of complications. The mean follow-up period was 85.05 ± 32.17 months (range 14–200). After operation, IOP dropped significantly from 35.76 ± 9.44 mmHg (mean ± SD) to 16.18 ± 7.20 mmHg together with a significant reversal of optic disc cupping. Similarly, the use of antiglaucoma medications was also significantly reduced in number from 1.26 ± 0.50 to 0.43 ± 0.70. Most of the axial lengths of the eyes measured at the last follow-up visit showed growths within the average ± 2 SDs in comparison with the healthy, age-matched population. After surgery, the qualified success rate was 90.77% at the end of the first year, 90.77% at the second year, 87.64% at the fifth year, 84.51% at the 10th year, and 81.38% at the 15th year. No serious intraoperative or postoperative complications were found. For Taiwanese children, the combined trabeculotomy–trabeculectomy using the modified Safer Surgery System offered an efficient and safe surgical option for treating glaucoma with long-term satisfactory control of IOP.

Purpose: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. Methods: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit. Disruption of actin stress fibers was measured in primary porcine TM cells and disruption of focal adhesions in transformed human TM (HTM) cells. Induction of fibrosis markers after exposure to transforming growth factor-β2 (TGF-β2) was conducted in primary HTM cells. Ocular hypotensive activity and tolerability of topical formulations were evaluated in normotensive Dutch Belted rabbits and Formosan Rock monkeys. In vitro corneal metabolism assays were conducted using dog, pig, rabbit, monkey, and human corneas. In vivo ocular pharmacokinetics was studied in Dutch Belted rabbits. Results: Netarsudil inhibited kinases ROCK1 and ROCK2 with a Ki of 1 nM each, disrupted actin stress fibers and focal adhesions in TM cells with IC50s of 79 and 16 nM, respectively, and blocked the profibrotic effects of TGF-β2 in HTM cells. Netarsudil produced large reductions in IOP in rabbits and monkeys that were sustained for at least 24 h after once daily dosing, with transient, mild hyperemia observed as the only adverse effect. Conclusion: Netarsudil is a novel ROCK/NET inhibitor with high potency in biochemical and cell-based assays, an ability to produce large and durable IOP reductions in animal models, and favorable pharmacokinetic and ocular tolerability profiles.

Purpose The purpose of this study was to develop a preclinical compound, ITRI-E-(S)4046, a dual synergistic inhibitor of myosin light chain kinase 4 (MYLK4) and Rho-related protein kinase (ROCK), for reducing intraocular pressure (IOP). Methods ITRI-E-(S)4046 is an amino-pyrazole derivative with physical and chemical properties suitable for ophthalmic formulation. In vitro kinase inhibition was evaluated using the Kinase-Glo Luminescent Kinase Assays. A comprehensive kinase selectivity analysis of ITRI-E-(S)4046 was performed using the KINOMEscan assay from DiscoverRx. The IOP reduction and tolerability of ITRI-E-(S)4046 were assessed in ocular normotensive rabbits, ocular normotensive non-human primates, and ocular hypertensive rabbits. In vivo studies were conducted to assess drug concentrations in ocular tissue. The adverse ocular effects of rabbit eyes were evaluated following the OECD405 guidelines. Results ITRI-E-(S)4046 showed highly selective kinase inhibitory activity against ROCK1/2, MYLK4, and mitogen-activated protein kinase kinase kinase 19 (MAP3K19), with high specificity against protein kinase A, G, and C families. In ocular normotensive rabbits and non-human primates, the mean IOP reductions of 0.1% ITRI-E-(S)4046 eye drops were 29.8% and 28.5%, respectively. In hypertonic saline-induced and magnetic beads-induced ocular hypertensive rabbits, the mean IOP reductions of ITRI-E-(S)4046 0.1% eye drops were 46.9% and 22.0%, respectively. ITRI-E-(S)4046 was well tolerated with only temporary and minor signs of hyperemia. Conclusions ITRI-E-(S)4046 is a novel type of highly specific ROCK1/2 and MYLK4 inhibitor that can reduce IOP in normotensive and hypertensive animal models. It has the potential to become an effective and well-tolerated treatment for glaucoma.

The aim of this study was to investigate whether exogenous erythropoietin (EPO) administration attenuates N-methyl-D-aspartate (NMDA)-mediated excitotoxic retinal damage in Wistar rats. The survival rate of retinal ganglion cells (RGCs) were investigated by flat mount analysis and flow cytometry. A total of 125 male Wistar rats were randomly assigned to five groups: negative control, NMDA80 (i.e., 80 nmoles NMDA intravitreally injected), NMDA80 + 10ng EPO, NMDA80 + 50ng EPO, and NMDA80 + 250ng EPO. The NMDA80 + 50ng EPO treatment group was used to evaluate various administrated points (pre-/co-/post- administration of NMDA80). Meanwhile, the transferase dUTP Nick-End Labeling (TUNEL) assay of RGCs, the inner plexiform layer (IPL) thickness and the apoptotic signal transduction pathways of μ-calpain, Bax, and caspase 9 were assessed simultaneously using an immunohistochemical method (IHC). When EPO was co-administered with NMDA80, attenuated cell death occurred through the downregulation of the apoptotic indicators: μ-calpain was activated first (peak at ~18hrs), followed by Bax and caspase 9 (peak at ~40hrs). Furthermore, the images of retinal cross sections have clearly demonstrated that thickness of the inner plexiform layer (IPL) was significantly recovered at 40 hours after receiving intravitreal injection with NMDA80 and 50ng EPO. Exogenous EPO may protect RGCs and bipolar cell axon terminals in IPL by downregulating apoptotic factors to attenuate NMDA-mediated excitotoxic retinal damage.

This study aimed to characterize the changes in the visual field (VF) patterns and disc morphology of patients with thyroid-associated orbitopathy (TAO) and open-angle glaucoma (OAG). A retrospective review of the medical records at the Tri-Service General Hospital in Taiwan identified 396 eyes of 198 patients with thyroid-associated glaucoma. A final follow-up of VF examination in 140 eyes revealed 114 eyes with VF defects, indicating disease progression. The characteristics of and changes in disc morphology, optical coherence tomography findings, and VF defects were statistically analyzed. The most common VF defects at the initial diagnosis and the end of the follow-up period were inferior partial arcuate (17%) and paracentral (15%) defects, respectively. The most common VF defect in patients with unspecific disc signs was an unspecific scotoma (13%). The most common optic disc feature was disc cupping (51%), followed by parapapillary atrophy (48%). The most frequent location of nerve fiber layer thinning was the inferotemporal region (48%). VF defects showed a significantly more pronounced progression in the non-nerve fiber bundle group than in the nerve fiber bundle group (p &lt, 0.001). This study details the characteristics and progression of disc morphology and VF defects in patients with TAO and OAG.

The overall goal of treating age-related macular degeneration (AMD) is to target the underlying cause of the disease and prevent, or at least slow down, the loss of vision, which requires the preservation of the choroid, retinal pigment epithelium (RPE), and photoreceptors. At present, there is no proven drug treatment for dry AMD; however, the cessation of smoking and treatments based on the age-related eye diseases study vitamin formula combined with a healthy diet are considered the only options for slowing disease progression. A number of pharmaceutical agents are currently under evaluation for the treatment of dry AMD using strategies such as reduction RPE and photoreceptor loss, neuroprotection, visual cycle modulators, suppression of inflammation, prevention of oxidative damage, and choroidal perfusion enhancers. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.Participants: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.Methods: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (−111.6 μm) and DEX implant 0.35 mg (−107.9 μm) than sham (−41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

Purpose The purpose of this study was to investigate the IOP-lowering effects of the ITRI-E-212, a new Rho-associated protein kinase (ROCK) inhibitor. ITRI-E-212 improved fluid outflow through the trabecular meshwork and reduced IOP with transient and mild conjunctival hyperemia. ITRI-E-212 can potentially be developed into new antiglaucoma agents. Methods ITRI-E-212 was selected from more than 200 amino-isoquinoline structures because of its adequate solubility and drug-loading percentage in eye drops. ITRI-E-212 has less than 50% inhibitory concentration (IC50) against ROCK2. The in vitro kinase inhibition was evaluated using the ADP-Glo kinase assay. A comprehensive analysis of the kinase inhibitor selectivity of ITRI-E-212 was performed using the KINOMEscan methodology. The IOP-lowering effect and tolerability of ITRI-E-212 were investigated in normotensive and ocular hypertensive rabbits. The pharmacokinetics study was performed in vivo in the aqueous humor (AH), and hyperemia was assessed. Results ITRI-E-212 showed high in vitro inhibitory activity against ROCK2 and high specificity against AGC kinases. The mean IOP-lowering effect of ITRI-E-212 in normotensive and ocular hypertensive models was 24.9% and 28.6%, respectively; 1% ITRI-E-212 produced notable reductions in IOP that were sustained for at least 6 hours after each dose once per day. Only transient, mild hyperemia was observed. The compound extracted from the AH reached 78.4% ROCK2 kinase inhibition at 1 hour after dose administration and was sustained for 4 hours. Conclusions ITRI-E-212 is a novel and highly specific ROCK2 inhibitor with the ability to lower IOP in animal models. It has favorable pharmacokinetic and ocular tolerability profiles with only minimal conjunctival hyperemia.

Age-related macular degeneration (AMD) is a vision-threatening age-associated disease. The retinal pigment epithelial (RPE) cells phagocytose and digest photoreceptor outer segment (POS). Incomplete digestion of POS leads to lipofuscin accumulation, which contributes to the pathology of the AMD. Autophagy could help reduce the amount of lipofuscin accumulation. In the present study, we evaluated the effects of glucosamine (GlcN), a natural supplement, on the induction of autophagy and POS-derived lipofuscin-like autofluorescence (LLAF) in ARPE-19 cells in vitro, and investigated the potential molecular pathway involved. Our results revealed that GlcN had no effect on phagocytosis of POS at the lower doses. GlcN treatment induced autophagy in cells. GlcN decreased the LLAF in native POS-treated cells, whereas malondialdehyde or 4-hydroxynonenal-modified POS attenuated this effect. 3-Methyladenine inhibited GlcN-induced autophagy and attenuated the effect of GlcN on the decrease of the native POS-derived LLAF. Furthermore, GlcN induced the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR), whereas Compound C inhibited these effects of GlcN. Altogether, these results suggest that GlcN decreased the native POS-derived LLAF through induction of autophagy, at least in part, by the AMPK–mTOR pathway. This mechanism has potential for the preventive treatment of lipofuscin-related retinal degeneration such as AMD.

Purpose Anterior uveitis is the most common ocular manifestation of sarcoidosis. Ocular involvement affects approximately 30–60% of patients with systemic sarcoidosis; however, optic disc edema is a rare event. We report a patient who presented with a rare case of sarcoidosis with neuro-ophthalmic manifestations. Case report A 22-year-old man was referred to our clinic with the primary complaint of a visual field defect over the temporal side of his right eye of 2 months duration. He did not have a history of systemic disease. At the first ophthalmic examination, the visual acuity, intraocular pressure, and slit lamp examination were normal. The fundus examination revealed bilateral optic disc edema. He was initially suspected of having a choroidal lesion between the disc and fovea of the right eye. To evaluate the possible lesion, the patient underwent brain magnetic resonance imaging (MRI), chest radiography, and chest computed tomography (CT). There were no abnormalities on the brain MRI, but the chest radiographs and CT images revealed bilateral mediastinal and hilar lymphadenomegaly. Histopathologic evaluation of an ultrasound-guided lymph node biopsy confirmed the diagnosis of sarcoidosis. Conclusion Neuro-ophthalmic manifestations of sarcoidosis are rare but may be the only presenting sign of an otherwise occult disease. A high clinical suspicion for sarcoidosis and its inclusion as a differential diagnosis are key to establishing the diagnosis and proper treatment.

Rationale: Vogt–Koyanagi–Harada (VKH) syndrome is a rare disease and could be associated with autoimmune thyroid disease (AITD). This report was aimed to investigate the utility of 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the diagnosis of VKH syndrome with AITD and to perform a literature review on the association between the 2 diseases. Patient concerns: A 55-year-old woman without the history of ocular trauma suffered from chronic headache. She was presented with painful blurred vision of both eyes with headache for 2 weeks. Ophthalmic evaluations revealed panuveitis, exudative retinal detachment, and papilloedema in both eyes. The clinical symptoms and presentations are compatible with the diagnosis of VKH syndrome. Other examinations for intraocular infection, malignancy, and lupus choroidopathy were of negative results. The result of contrast-enhanced computed tomography (CT) of the brain was normal. Due to the history of cancer in the patient's families, a 18F-FDG PET/CT whole-body scan was performed. The result indicated a focal of 2-fluoro-2-deoxy-d-glucose (FDG) uptake at the right upper lobe of the thyroid. Therefore, the patient's thyroid function was examined and the result indicated euthyroidism with detectable thyroid peroxidase/thyroglobulin antibodies. Diagnoses: VKH syndrome with associated AITD. Interventions: Treatment with intravenous pulse systemic methylprednisolone (1000 mg daily) was prescribed for 3 days and then shifted gradually to tapered oral steroid medication. Outcomes: Symptoms of papillitis and serous retinal detachment of VKH syndrome was relieved after steroid treatment Lessons: 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can be used for the effective diagnosis of VKH syndrome with AITD.

To evaluate the effects of silibinin on intercellular adhesion molecule-1 (ICAM-1) expression, we used ARPE-19 cells as a model in which tumor necrosis factor (TNF-α) and interferon (IFN-γ) enhanced ICAM-1 expression. This upregulation was inhibited by silibinin. In an adherence assay using ARPE-19 and THP-1 cells, silibinin inhibited the cell adhesion function of ICAM-1. The inhibitory effects of silibinin on ICAM-1 expression were mediated via the blockage of nuclear translocation of p65 proteins in TNF-αand phosphorylation of STAT1 in IFN-γ-stimulated cells. In addition, silibinin altered the degree of N-linked glycosylation posttranslationally in ARPE-19 cells by significantly enhancingMGAT3gene expression. Silibinin can increase the O-GlcNAc levels of glycoproteins in ARPE-19 cells. In a reporter gene assay, PUGNAc, which can also increase O-GlcNAc levels, inhibited NF-κB reporter activity in TNF-α-induced ARPE-19 cells and this process was augmented by silibinin treatment. Overexpression ofOGTgene was associated with reduced TNF-α-induced ICAM-1 levels, which is consistent with that induced by silibinin treatment. Taken together, silibinin inhibits ICAM-1 expression and its function through altered O-linked glycosylation in NF-κB and STAT1 signaling pathways and decreases the N-linked glycosylation of ICAM-1 transmembrane protein in proinflammatory cytokine-stimulated ARPE-19 cells.