Treatment Of Ocular Hypertension Research Articles

Treatment of Open-Angle Glaucoma and Ocular Hypertension with the Fixed-Dose Combination of Preservative-Free Tafluprost/Timolol: Clinical Outcomes from Ophthalmology Clinics in Italy.

IntroductionThe VISIONARY study examined the intraocular pressure (IOP)-lowering efficacy and tolerability of the preservative-free fixed-dose combination of tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in a real-world setting. The country-level data reported herein comprise the largest and first observational study of PF tafluprost/timolol FC therapy in Italy.MethodsAn observational, multicenter, prospective study included adult Italian patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) demonstrating insufficient response or poor tolerability with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Treatment was switched to PF tafluprost/timolol FC therapy at baseline. Primary endpoint was the absolute mean IOP change from baseline at Month 6. Exploratory and safety endpoints included change in IOP at Weeks 4 and 12, ocular signs, symptom severity and reporting of adverse events (AEs).ResultsOverall, 160 OAG/OHT patients were included. Mean ± standard deviation IOP was reduced from 19.6 ± 3.6 mmHg at baseline to 14.5 ± 2.6 mmHg at Month 6 (reduction of 5.1 ± 3.7 mmHg; 24.1%; p < 0.0001). IOP reduction was also statistically significant at Week 4 (23.1%; p < 0.0001) and Week 12 (24.7%; p < 0.0001). Based on data cutoff values for mean IOP change of ≥20%, ≥25%, ≥30% and ≥35%, respective Month 6 responder rates were 68.1%, 48.7%, 36.2% and 26.9%. Most ocular signs and symptoms were significantly reduced in severity from baseline at Month 6. Two non-serious and mild AEs were reported during the study period, among which, one AE was treatment-related (eyelash growth). ConclusionItalian OAG and OHT patients demonstrated a significant IOP reduction from baseline at Week 4 that was maintained over a 6-month period following a switch from topical PGA or beta-blocker monotherapy to PF tafluprost/timolol FC therapy. Severity of most ocular signs and symptoms was significantly reduced during the study period, and PF tafluprost/timolol FC was generally well tolerated.

Prevalence of Ocular Hypertension in Patients Above 40 Years of Age

Introduction: Ocular hypertension is a condition with elevated intraocular pressure that needs to be monitored closely to prevent glaucoma and other complications. The study aims to find out the prevalence of ocular hypertension in patients aged more than 40 years. Materials and methods: This is a hospital based cross-sectional study conducted in a community based tertiary hospital of Nepal. Results: Mean age of the patients was 47.53years. 62% of the patients were males and 38% were females. Mean intraocular pressure in the right eye was 15.8 mmHg and mean intraocular pressure in left eye was 16.2 mm Hg. Prevalence of ocular hypertension was 6%. Conclusion: All patients more than 40 years of age should undergo detailed ocular examination for early detection and treatment of ocular hypertension.

The Impact of Systemic Health Parameters on Intraocular Pressure in the Western Region of Saudi Arabia.

BackgroundA normal intraocular pressure (IOP) is essential for maintaining the normal structure and function of the eyes. Furthermore, an elevated IOP is a known risk factor for glaucoma. As the results from studies addressing the relationship between IOP and systemic health parameters are conflicting, researchers have not reached a consensus. This study aimed to evaluate the relationship between IOP and health parameters among non-glaucomatous participants in the western region of Saudi Arabia.MethodWe retrospectively reviewed the medical records of 255 participants aged 20 years and above who had not received any medical treatment for ocular hypertension or glaucoma at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, from January 2019 to April 2021. The patients were categorized into age groups, divided by decades (ranging from 20-29 years to 80+ years); the most prevalent age group was 60-69 years. The data were entered using Microsoft Excel 2016 (Microsoft Corporation, Redmond, Washington), and Statistical Package for the Social Sciences (SPSS) software was used for univariate analysis. The relationship between continuous variables was analyzed by the Pearson correlation coefficient. The differences between continuous and categorical variables were assessed by the t-test and one-way analysis of variance (ANOVA) test, respectively.ResultsThe mean (standard deviation) IOP in the right and the left eyes was 15.7 mmHg (4.0) and 15.6 mmHg (3.9), respectively. There were no significant associations between IOP and lipid profile parameters (p > 0.05). There was a statistically significant difference in the right IOP, in relation to the age groups (p = 0.006). Moreover, the mean IOP in the left eye was significantly higher among patients with diabetes than in the patients without diabetes (p = 0.007) as well as in patients with hypertension than in the patients without hypertension (p = 0.023).ConclusionThe effect of total cholesterol, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), BMI, and sex on IOP could not be established in our study. However, over the past years, people's diets have incorporated higher cholesterol and fat content, leading to higher BMI levels. Therefore, further studies of the association between BMI and IOP are critical to determine if BMI is certainly a significant risk factor for increased IOP and glaucoma.

Switching to Preservative-Free Tafluprost/Timolol Fixed-Dose Combination in the Treatment of Open-Angle Glaucoma or Ocular Hypertension: Subanalysis of Data from the VISIONARY Study According to Baseline Monotherapy Treatment.

IntroductionThe VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy.MethodsA European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6.ResultsThe subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (p < 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7 (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup (p = 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users (p < 0.001).ConclusionPF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively.Clinical Study NumberEuropean Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02166-6.

Incidence, Risk Factors, Treatment, and Outcome of Ocular Hypertension following Intravitreal Steroid Injections: A Comparative Study

Purpose: To compare the incidence, risk factors, treatment, and outcomes associated with intravitreal triamcinolone-acetonide (TA) and dexamethasone-implant (Dex)-induced ocular hypertension (OHT). Methods: This retrospective study reviewed 1,549 TA and Dex administrations in 1,075 eyes of 897 patients. Intraocular pressure (IOP) values were monitored for a period of 6 months following intravitreal injection(s) and patients were categorized as steroid-responders (SR): IOP≥21 mm Hg, and steroid non-responders (NR): IOP≤20 mm Hg. Glaucoma patients, glaucoma suspects, uveitis, trauma, and less than 1 month of IOP follow-up cases were excluded from the study. The incidence of IOP rise, time and magnitude of IOP rise, and its management procedures were studied. Ocular and systemic associations with OHT incidence were investigated. Statistical analysis was performed using SPSS.23 and p < 0.05 was considered significant. Result: Twenty-eight percent of TA and 17% of Dex administered eyes developed OHT. Male subjects and elderly people (greater than 40 years of age) are at higher risk for OHT following steroid treatment. A high percentage of IOP rise was observed on day 1 (41%) for TA-SR, and after 1 month (50%) for Dex-SR. IOP rise was found to be more severe (>30 mm Hg) for TA-SR compared to Dex-SR (p = 0.006). 6% TA-SR required trabeculectomy with medically uncontrollable IOP. Myopia is a risk factor for secondary OHT, whereas diabetes mellitus and hypercholesterolemia are protective of it. Conclusion: Twenty-eight percent of TA and 17% of Dex administrations developed OHT. Early and severe IOP rises were more common in TA than among Dex administrations. Myopia is a risk for Dex-OHT.

Treatment of open-angle glaucoma and ocular hypertension with preservative-free tafluprost/timolol fixed-dose combination therapy: 6 case reports and clinical outcomes

BackgroundTreatment of open angle glaucoma (OAG) and/or ocular hypertension (OHT) focuses on achievement of target intraocular pressure (IOP), with the objective of slowing disease progression. However, ocular surface health is an important consideration in the optimization of treatment. We report 6 patient cases in which enhanced IOP control was achieved following appropriate management of ocular surface inflammation and a therapeutic switch to the preservative-free (PF) tafluprost (0.0015%)/timolol (0.5%) fixed-dose combination (FC).Case presentationSix patient cases, aged 48–74 years, presented with OAG or OHT. Each patient had signs and symptoms of ocular surface disease (OSD). Cases 1–3 were each receiving maximal medical therapy for OAG; regimens comprising prostaglandin analogue (PGA), β-blocker, carbonic anhydrase inhibitor (CAI) and α-2 agonist agents (including treatments containing preservative agent). Cases 1 and 2 reported IOP values ≥23 mmHg in each eye, and wide IOP fluctuations were identified when reviewing patient data concerning case 3 (11–20 mmHg). Maximal therapy was ceased and PF tafluprost/timolol FC was initiated, after which the signs and symptoms of OSD were improved and IOP was reduced (≤18 mmHg for cases 1–3) and stabilized. Cases 4 and 5 were diagnosed with OAG and case 6 had OHT. Each had symptoms and signs of OSD and were treated with a preserved PGA monotherapy (latanoprost 0.005% or bimatoprost 0.03%). At presentation, IOP was 24 mmHg in both eyes (case 4), ≥18 mmHg (case 5) and ≥ 22 mmHg (case 6). Following a switch to the PF tafluprost/timolol FC, OSD symptoms were improved and IOP was 14 mmHg (both eyes; case 4), ≤14 mmHg (case 5) and 16 mmHg (both eyes; case 6).ConclusionsIn addition to IOP-lowering efficacy, approaches to the management of OAG and OHT should consider the impact of treatment tolerability and the susceptibility of these patients to OSD. The presence of ocular surface inflammation appears to be detrimental to adherence and therefore to the effectiveness of topical medications. Addressing OSD through the use of PF FC formations, such as the PF tafluprost/timolol FC, reduces exposure to potentially toxic agents and facilitates improvements in IOP control.

Efficacy and Patient Tolerability of Omidenepag Isopropyl in the Treatment of Glaucoma and Ocular Hypertension.

Current therapeutic approaches for glaucoma aim to reduce intraocular pressure (IOP), which is the only available and reliable strategy proven to control the risk of disease development and progression. Omidenepag isopropyl (OMDI) is a novel topical ocular hypotensive agent that was launched onto the market for the treatment of glaucoma and ocular hypertension (OHT). After topical instillation and during corneal penetration, OMDI is converted into the active metabolite omidenepag (OMD), which behaves as a non-prostaglandin, selective E-prostanoid subtype 2 (EP2) receptor agonist. The topical administration of 0.002% OMDI once-daily (QD) possesses a 20–35% IOP-lowering effect, comparable to that of prostaglandin analogs targeting F-prostanoid (FP) receptor QD, which are the current first-line for pharmaceutical reduction of IOP. However, the mechanism of action and adverse events (AEs) of OMDI are different from those of FP receptor agonists. OMDI reduces IOP by enhancing both conventional trabecular and uveoscleral outflow facilities without complications of prostaglandin-associated periorbitopathy (PAP) seen with FP receptor agonists. Moreover, OMDI was also effective and well-tolerated in non-/poor responders to latanoprost and showed a stable IOP-lowering effect for one year, and its concomitant use with timolol enhanced the IOP-lowering effect. OMDI demonstrated acceptable safety and tolerability with good adherence and can be used in almost every patient. However, OMDI has some AEs such as conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema and ocular inflammation. Moreover, OMDI is contraindicated in patients who are allergic to the product, in aphakic or pseudophakic eyes, and in combination with tafluprost eye drops. If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and OHT as a first-line alternative to FP agonists. Here, we summarize the results of clinical studies of OMDI and discuss its efficacy and patient tolerability in glaucoma and OHT in this review.

Detecting Glaucoma in the Ocular Hypertension Study Using Deep Learning

Automated deep learning (DL) analyses of fundus photographs potentially can reduce the cost and improve the efficiency of reading center assessment of end points in clinical trials. To investigate the diagnostic accuracy of DL algorithms trained on fundus photographs from the Ocular Hypertension Treatment Study (OHTS) to detect primary open-angle glaucoma (POAG). In this diagnostic study, 1636 OHTS participants from 22 sites with a mean (range) follow-up of 10.7 (0-14.3) years. A total of 66 715 photographs from 3272 eyes were used to train and test a ResNet-50 model to detect the OHTS Endpoint Committee POAG determination based on optic disc (287 eyes, 3502 photographs) and/or visual field (198 eyes, 2300 visual fields) changes. Three independent test sets were used to evaluate the generalizability of the model. Areas under the receiver operating characteristic curve (AUROC) and sensitivities at fixed specificities were calculated to compare model performance. Evaluation of false-positive rates was used to determine whether the DL model detected POAG before the OHTS Endpoint Committee POAG determination. A total of 1147 participants were included in the training set (661 [57.6%] female; mean age, 57.2 years; 95% CI, 56.6-57.8), 167 in the validation set (97 [58.1%] female; mean age, 57.1 years; 95% CI, 55.6-58.7), and 322 in the test set (173 [53.7%] female; mean age, 57.2 years; 95% CI, 56.1-58.2). The DL model achieved an AUROC of 0.88 (95% CI, 0.82-0.92) for the OHTS Endpoint Committee determination of optic disc or VF changes. For the OHTS end points based on optic disc changes or visual field changes, AUROCs were 0.91 (95% CI, 0.88-0.94) and 0.86 (95% CI, 0.76-0.93), respectively. False-positive rates (at 90% specificity) were higher in photographs of eyes that later developed POAG by disc or visual field (27.5% [56 of 204]) compared with eyes that did not develop POAG (11.4% [50 of 440]) during follow-up. The diagnostic accuracy of the DL model developed on the optic disc end point applied to 3 independent data sets was lower, with AUROCs ranging from 0.74 (95% CI, 0.70-0.77) to 0.79 (95% CI, 0.78-0.81). The model's high diagnostic accuracy using OHTS photographs suggests that DL has the potential to standardize and automate POAG determination for clinical trials and management. In addition, the higher false-positive rate in early photographs of eyes that later developed POAG suggests that DL models detected POAG in some eyes earlier than the OHTS Endpoint Committee, reflecting the OHTS design that emphasized a high specificity for POAG determination by requiring a clinically significant change from baseline.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: Results from the VISIONARY Study Population in Spain.

Purpose:Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in the treatment of OAG and OHT.Methods:An observational, multicenter prospective study examined treatment outcomes following a switch to PF tafluprost/timolol FC in adult OAG/OHT patients demonstrating insufficient response to beta-blocker or prostaglandin analog (PGA) monotherapy. Primary end point was mean change in intraocular pressure (IOP) from baseline at month 6. Changes in the severity of ocular signs and symptoms were also assessed.Results:Overall, 92 patients (51.1% female) were included. Mean (standard deviation) age was 68.3 (12.1) years. Mean IOP was reduced from 21.9 mmHg at baseline to 16.7 mmHg at month 6 (22.3% decrease; P < 0.0001). Significant IOP reductions were observed at weeks 4 and 12 (P < 0.0001). Baseline PGA and beta-blocker users demonstrated mean month 6 IOP reductions of 5.5 mmHg (23.5%; P < 0.001) and 3.5 mmHg (14.6%; P = 0.029), respectively. Severity of conjunctival hyperemia, dry eye, irritation, itching, foreign body sensation, and eye pain was significantly reduced. Three treatment-related adverse events were reported, all were nonserious and mild/moderate in severity.Conclusion:In real-world clinical practice, PF tafluprost/timolol FC treatment provided significant IOP reductions over 6 months and was well tolerated among OAG/OHT patients showing poor response to PGA or beta-blocker monotherapy. IOP-lowering efficacy and improvements in ocular signs and symptoms were evident from week 4 and maintained over the 6-month study period. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number EUPAS22204.

Cost-Utility Analysis of a Latanoprost Cationic Emulsion (STN1013001) versus Other Latanoprost in the Treatment of Open-Angle Glaucoma or Ocular Hypertension and Concomitant Ocular Surface Disease in Germany.

PurposeThis study aimed to estimate the cost–utility and economic value of STN1013001, a latanoprost cationic emulsion vs other latanoprost formulations (henceforth latanoprost) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and concomitant ocular surface disease (OSD) in Germany.MethodsAn early 5-year Markov model-supported cost–utility analysis was performed to estimate costs, quality-adjusted life years (QALYs) and life-years saved (LYS) for STN1013001 vs latanoprost from the German health system perspective. The model included seven mutually exclusive health states and adopted a 1-year cycle length. The model was populated with pooled data derived, by means of a questionnaire, from a convenience sample of five German glaucoma specialists. Remaining data were derived from published sources. Data provided by the ophthalmologists included annual treatment adherence probabilities, utility values and resource utilization. The half-cycle correction as well as a discount rate of 3.0% per year were applied to costs (expressed in €2020), life-year saved (LYS) and QALYs. The incremental cost–utility ratio (ICUR) was contrasted against the informal willingness-to-pay (WTP) threshold for incremental LYS saved or QALY gained (€30,000) proposed for Germany. One-way and probabilistic sensitivity analyses (OWSA; PSA) tested the robustness of the base case ICUR.ResultsOver the 5-year time horizon, STN1013001 strongly dominates latanoprost as it is less costly (€1003.65 vs €1145.37; −12.37%) and produces more QALYs (2.612 vs 2.365; +10.44%) per notional patient. Baseline findings were robust against all the variations included in OWSA. PSA shows that STN1013001 has a 100% probability of being cost-effective vs Latanoprost at each WTP threshold for incremental QALY gained.ConclusionOnce on the market, STN1013001 will provide a cost-effective and possibly strongly dominant therapy vs latanoprost for OAG/OHT+OSD patients from a German health system perspective. Future empirical research should confirm these findings.

Treatment of open angle glaucoma or ocular hypertension with preservative‐free tafluprost/timolol fixed dose combination in a real‐world setting: analysis by diagnostic sub‐group at study entry

AbstractPurposeThe VISIONARY study assessed the efficacy of the preservative‐free tafluprost/timolol fixed‐dose combination (PF tafluprost/timolol FC) in patients with open‐angle glaucoma (OAG) or ocular hypertension (OHT) who were inadequately controlled with prostaglandin analogue (PGA) or beta‐blocker (BB) monotherapy. This analysis examined IOP reduction by diagnosis and prior treatment type.MethodsIOP was recorded at baseline for adults (≥18 years) receiving topical PGA or BB monotherapy for OAG/OHT and treatment was switched to PF tafluprost/timolol FC. IOP was recorded at Weeks 4, 12 and 24. The primary endpoint was mean absolute change in IOP from baseline at Month 6. Baseline diagnoses were OHT (n = 110), primary open‐angle glaucoma (POAG; n = 425), normal tension glaucoma (NTG; n = 13), or pseudoexfoliative glaucoma (PEX; n = 19).ResultsMean (SD) baseline IOP was 21.5 (5.00) mmHg, 22.3 (4.30) mmHg, 17.2 (2.68) mmHg and 21.7 (4.13) mmHg for patients with POAG, OHT, NTG and PEX, respectively. Respective Month 6 relative IOP reductions were 25.4%, 26.1%, 15.8% and 17.6%. Mean (SD) baseline IOP was 21.9 (4.36) mmHg and 21.4 (4.48) mmHg for BB and PGA users, respectively. Month 6 respective IOP reduction from baseline was 6.6 (4.16) mmHg (28.5%) and 5.4 (4.04) mmHg (23.6%) (p &lt; 0.0001). PF tafluprost/timolol FC was generally well tolerated; 14 patients discontinued due to poor local tolerance or insufficient IOP control.ConclusionsIn this real‐world study, PF tafluprost/timolol FC was effective and well‐tolerated in patients previously uncontrolled on BB or PGA monotherapy, irrespective of initial diagnosis and type of previous topical medication. Patients with OHT, POAG, NTG and PEX showed IOP reductions at Week 4 that were maintained throughout the study period.BibliographyOddone F, et al. Treatment of Open‐Angle Glaucoma and Ocular Hypertension with Preservative‐Free Tafluprost/Timolol Fixed‐Dose Combination Therapy: The VISIONARY Study. Adv Ther.2020;37(4):1436–51.

Multi-scale Multi-structure Siamese Network (MMSNet) for Primary Open-Angle Glaucoma Prediction.

Primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness in the United States and worldwide. POAG prediction before onset plays an important role in early treatment. Although deep learning methods have been proposed to predict POAG, these methods mainly focus on current status prediction. In addition, all these methods used a single image as input. On the other hand, glaucoma specialists determine a glaucomatous eye by comparing the follow-up optic nerve image with the baseline along with supplementary clinical data. To simulate this process, we proposed a Multi-scale Multi-structure Siamese Network (MMSNet) to predict future POAG event from fundus photographs. The MMSNet consists of two side-outputs for deep supervision and 2D blocks to utilize two-dimensional features to assist classification. The MMSNet network was trained and evaluated on a large dataset: 37,339 fundus photographs from 1,636 Ocular Hypertension Treatment Study (OHTS) participants. Extensive experiments show that MMSNet outperforms the state-of-the-art on two "POAG prediction before onset" tasks. Our AUC are 0.9312 and 0.9507, which are 0.2204 and 0.1490 higher than the state-of-the-art, respectively. In addition, an ablation study is performed to check the contribution of different components. These results highlight the potential of deep learning to assist and enhance the prediction of future POAG event. The proposed network will be publicly available on https://github.com/bionlplab/MMSNet.

The Application of Nitric Oxide for Ocular Hypertension Treatment.

Despite of various therapeutic methods for treating ocular hypertension and glaucoma, it still remains the leading cause of irreversible blindness. Intraocular pressure (IOP) lowering is the most effective way to slow disease progression and prevent blindness. Among the ocular hypotensive drugs currently in use, only a couple act on the conventional outflow system, which is the main pathway for aqueous humor outflow and the major lesion site resulting in ocular hypertension. Nitric oxide (NO) is a commendable new class of glaucoma drugs that acts on the conventional outflow pathway. An increasing number of nitric oxide donors have been developed for glaucoma and ocular hypertension treatment. Here, we will review how NO lowers IOP and the types of nitric oxide donors that have been developed. And a brief analysis of the advantages and challenges associated with the application will be made. The literature used in this review is based on Pubmed database search using ‘nitric oxide’ and ‘glaucoma’ as key words.

Noninferiority Study Comparing Latanoprost 0.005% Without Versus With Benzalkonium Chloride in Open-Angle Glaucoma or Ocular Hypertension.

To evaluate the noninferiority of intraocular pressure (IOP)-lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension). Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 am, 10 am, and 4 pm). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for≥7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE). The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups. Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.

Structure/function/treatment in glaucoma: progress over the last 10years

Since the 1990s several so-called landmark studies were carried out, which played an important role in the management of glaucoma patients due to their multicenter, randomized and masked structure. The Ocular Hypertension Treatment Study (OHTS) and the Collaborative Initial Treatment Glaucoma Study (CIGTS) and their follow-up studies are especially important in the conservative glaucoma management and in the evaluation of structure and function. The OHTS examined if lowering of the intraocular pressure (IOP) treatment reduces the progression from ocular hypertension to primary open angle glaucoma and what risk factors influence the progression. The CIGTS examined the progression of glaucoma in patients treated either with pharmacotherapy or with surgery. The recent studies, the United Kingdom Glaucoma Treatment Study (UKGTS) and Glaucoma Automated Test Evaluation (GATE) investigated the influence of treatment with latanoprost on the development of visual field defects and examination of different screening tests in glaucoma, respectively. The OHTS provided results that justify prophylactic treatment as well as watchful waiting. The results of CIGTS showed that under certain conditions surgical treatment of a newly discovered glaucoma can be recommended for moderate to advanced glaucoma. In the UKGTS treatment with latanoprost reduced the intraocular pressure and also the progression of visual field defects in beginning and moderate glaucoma damage. The GATE study found no clear-cut advantage of screening examinations, with cost effectiveness and without a substantial proportion of diagnoses being missed.

Glaucomanet: A Deep-Learning Algorithm for the Diagnosis of Primary Open-Angle Glaucoma from Fundus Photographs

Background: Primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness in the United States and worldwide. Although deep learning methods have been proposed to diagnose POAG, it remains challenging to develop a robust and explainable algorithm to facilitate the downstream diagnostic tasks automatically. Methods: We proposed a deep learning model, GlaucomaNet, with joint fusion to identify POAG from fundus photographs. GlaucomaNet consists of two neural networks to simulate the human grading process: one performing preliminary grading and the other detailed grading. An ensemble of network architectures further improved diagnostic accuracy. GlaucomaNet was evaluated on two independent datasets. The performance was measured by AUC, accuracy, precision, sensitivity, specificity, and F1-score. Findings: GlaucomaNet was trained and evaluated on two datasets: 37,339 fundus photographs from the Ocular Hypertension Treatment Study (OHTS), and 4,855 fundus photographs from the Large-scale Attention-based Glaucoma (LAG) dataset. GlaucomaNet achieved superior performance to six state-of-the-art neural networks on OHTS, with accuracy of 0.930 (standard deviation, 0.010), F1-score of 0.490 (0.033), and AUC of 0.904 (0.014). It also outperformed the baselines on the LAG dataset. Interpretations: GlaucomaNet demonstrated high accuracy with increased transparency in POAG diagnosis. It is also applicable for two well-known challenges: image data diversity and POAG only due to visual fields abnormalities. These results highlight the potential of deep learning to assist and enhance clinical POAG diagnosis. GlaucomaNet is publicly available on https://github.com/bionlplab/GlaucomaNet. Funding: This project was supported by the National Library of Medicine (4R00LM013001), the National Eye Institute, the National Center on Minority Health and Health Disparities (EY09341, EY09307) at NIH, Horncrest Foundation, the Department of Ophthalmology and Visual Sciences at Washington University, the NIH Vision Core Grant (P30EY02687), Merck Research Laboratories, Pfizer, Inc., White House Station, New Jersey, and unrestricted grants from Research to Prevent Blindness, Inc., New York, NY. Declaration of Interest: Ethical Approval: The first dataset is obtained from the Ocular Hypertension Treatment Study (OHTS). The OHTS comes from 22 centers in the United States. The study protocol was approved by an independent Institutional Review Board at each clinical center

Correlation Between Central Corneal Thickness and Radial Peripapillary Capillary Density, in Patients With Ocular Hypertension

PurposeTo investigate any possible relationship between the central corneal thickness and the radial peripapillary capillary density detected by optical coherence tomography (OCT) angiography in eyes with ocular hypertension.Materials and methodsIn this observational study, 135 eyes were examined. OCT angiography of the optic disc (4.5 mm) and ultrasound corneal pachymetry were performed in all cases. Age, medical treatment for ocular hypertension, sex, and retinal nerve fiber layer thickness were evaluated. The main indices of blood flow were also examined. Spearman correlation coefficients were used to explore the association between two continuous variables.ResultsA directly proportional significance regarding the correlation between central corneal thickness and radial peripapillary network was indicated in eyes with ocular hypertension (p = .036).ConclusionsCentral corneal thickness and radial peripapillary capillary density constitute two essential screening parameters for patients with ocular hypertension.

Normalisation process theory and the implementation of a new glaucoma clinical pathway in hospital eye services: Perspectives of doctors, nurses and optometrists

Normalisation process theory reports the importance of contextual integration in successfully embedding novel interventions, with recent propositions detailing the role that 'plasticity' of intervention components and 'elasticity' of an intended setting contribute. We report on the introduction of a clinical pathway assessing patient non-responsiveness to treatment for glaucoma and ocular hypertension. The aim of this study was to assess the feasibility of implementing the Cardiff Model of Glaucoma Care into hospital eye services, identifying any issues of acceptability for staff through the filter of normalisation process theory. A prospective observational study was undertaken in four hospital eye services. This incorporated detailed qualitative semi-structured interviews with staff (n = 8) to gather their perceptions on the intervention's usefulness and practicality. In addition, observational field notes of patient and staff consultations (n = 88) were collected, as well as broader organisational observations from within the research sites (n = 52). Data collection and analysis was informed by the normalisation process theory framework. Staff reported the pathway led to beneficial knowledge on managing patient treatment, but the model was sometimes perceived as overly prescriptive. This perception varied significantly based on the composition of clinics in relation to staff experience, staff availability and pre-existing clinical structures. The most commonly recounted barrier came in contextually integrating into sites where wider administrative systems were inflexible to intervention components. Flexibility will be the key determinant of whether the clinical pathway can progress to wider implementation. Addressing the complexity and variation associated with practice between clinics required a remodelling of the pathway to maintain its central benefits but enhance its plasticity. Our study therefore helps to confirm propositions developed in relation to normalisation process theory, contextual integration, intervention plasticity, and setting elasticity. This enables the transferability of findings to healthcare settings other than ophthalmology, where any novel intervention is implemented.

Quality of referrals for glaucoma assessment: a cross-sectional survey of clinical data and outcomes.

This study assessed the completeness of clinical information provided by ophthalmological and optometric referrals to glaucoma specialists consulting for open-angle glaucoma (OAG). A retrospective, cross-sectional study of 72 internal referrals for evaluation of OAG in a multispecialty group practice was performed. The quality of the referral was assessed based on: (1) the completeness of the clinical triad of intraocular pressure measurement, visual field (VF), and cup-to-disk ratio for each eye; (2) the availability of the data necessary to calculate an ocular hypertension treatment study (OHTS) score; and (3) the presence of retinal nerve fiber layer (RNFL) imaging by mean of optical coherence tomography. The clinical triad was available in 57% of referrals, whereas an OHTS score was calculable in 24% of referrals (p < 0.001); RNLF imaging was available in 51% of referrals (p = 0.859). The completeness of clinical information was similar for ophthalmological and optometric referrals. From the date of referral to the time of the consultation, there was a significant increase in the availability of the clinical triad (57-65%; p = 0.013) and the OHTS score (24-5%; p = 0.004) but not for RNFL imaging (51-56%; p = 0.618). The most common missing clinical information was VF testing, which was absent in 42% of referrals. Key clinical data necessary for effective diagnosis and staging of OAG was lacking for many patients referred to glaucoma specialists.

Selective Laser Trabeculoplasty in the Treatment of Ocular Hypertension and Open-Angle Glaucoma: Clinical Review.

Selective laser trabeculoplasty (SLT) is a glaucoma treatment that reduces intraocular pressure (IOP). Its mechanism is based on the biological effects of the selective application of laser energy to pigmented trabecular meshwork (TM) cells, resulting in increased outflow facility. Herein, we review current publications on SLT and summarize its efficacy and safety for different indications in open-angle glaucoma (OAG) and ocular hypertension (OHT) treatment. SLT effectively reduces IOP when used as a primary treatment. In patients whose IOP is medically controlled, SLT helps to reduce medication use, and when maximally tolerated topical therapy is ineffective, SLT facilitates the realization of the target IOP. SLT is a repeatable procedure for which the vast majority of complications are mild and self-limiting. With effective IOP reduction, low complication rates and the potential to repeat the procedure, SLT offers the possibility of delaying the introduction of medical therapy and other more invasive treatment modalities while simultaneously avoiding the accompanying complications. With this knowledge, we suggest that SLT be considered as an essential primary treatment option in OAG and OHT, switching to other treatment modalities only when laser procedures are insufficient for achieving the required target IOP.