Predictors and long-term patterns of medication adherence to glaucoma treatment in Denmark-an observational registry study of 30 100 Danish patients with glaucoma.

BACKGROUND: Self-treatment with glaucoma medication (eye drops) has been associated with adherence challenges. Poor adherence results in worse outcomes in terms of visual field loss. OBJECTIVE: To investigate patterns in medication adherence among Danish patients with glaucoma in relation to selected predictors of adherence, long-term adherence patterns, and long-term societal economic consequences of poor adherence. METHODS AND ANALYSIS: This register-based study included 30 100 glaucoma patients followed for 10 years between 2000 and 2018. Glaucoma was identified from the Danish national registers by diagnosis of Open Angle Glaucoma and/or by redeemed prescriptions of glaucoma medication. Logistic regression models were applied to estimate patient characteristics related to medical adherence. Diagnosis-related group fees were applied to estimate healthcare costs. RESULTS: High adherence in the first year(s) of treatment was less likely among men (ORfirst year: 0.78, 95% CI: 0.75 to 0.82), younger individuals and among those with a positive Charlson Comorbidity Index (CCI) score (ORfirst year/CCI≥3: 0.71, 95% CI: 0.63 to 0.80). Adherence in the first year and in the first two years was associated with adherence in the fifth (ORfirst year: 4.55, 95% CI: 4.30 to 4.82/ORfirst two years: 6.47, 95% CI: 6.10 to 6.86) as with adherence in the 10th year with slightly lower estimates. Being medical adherent was related to higher costs related to glaucoma medication after 5 and 10 years comparing with poor adherence, whereas poor adherence was associated with a marked increase in long-term costs for hospital contacts. CONCLUSION: Increasing age, female sex and low comorbidity score are correlated with better adherence to glaucoma treatment. Adherence in the first years of treatment may be a good predictor for future adherence. In the long term, patients with poor adherence are overall more expensive to society in terms of hospital contacts.

Minimally invasive micro sclerostomy (MIMS) procedure in the treatment of open-angle glaucoma.

BACKGROUND: To evaluate the safety and efficacy of the Minimally Invasive Micro Sclerotomy (MIMS) procedure in the management of uncontrolled open-angle glaucoma. METHODS: A prospective, open-label, single-arm clinical evaluation with intra-subject comparisons performed at the Ophthalmologic Center after S.V. Malayan, Yerevan, Armenia. Included were adults with primary open-angle glaucoma (OAG) (N = 114) or exfoliative glaucoma (N = 6) who were uncontrolled (IOP > 21) on tolerated topical medication. Mild (N = 7), moderate (N = 66) and severe (n = 47) cases were prospectively included without preselection. Following subconjunctival Mitomycin C, an ab-interno MIMS procedure was performed alone (N = 100) or combined with phacoemulsification (N = 20). Patients were followed for 52 weeks. Procedure-related complications and adverse events were recorded. Success criteria were defined as -5 < IOP ≤ 21mmHg OR a reduction in IOP of ≥ 20% from baseline with (qualified success) or without (complete success) hypotensive medications. RESULTS: Mean patient age was 69 ± 10.1 years. The mean duration of the procedure was 2:01 ± 0:41 min:sec. Scleral drainage channels were achieved in all cases. No device malfunctions, intraoperative complications, or serious adverse events were reported. Iris plugging of the sclerostomy site and early spikes in IOP were the most common adverse events. The only reason for failure was final IOP > 21 mmHg on tolerated medication. At 52 weeks (n = 93), mean IOP decreased by 38% from baseline (P < 0.001), from 27.9 ± 3.7 to 17.5 ± 5.3 mmHg, a difference of 10.5 mmHg (95% CI: -11.7, -9.3). One-year qualified success was documented in 82.1% (95% CI: 72.9%,89.2%) of the patients and complete success, in 70.5% (60.3-79.4%). 60% (95 CI:49.4%,69.9%) of the patients achieved maximum IOP level of 14 mmHg or at least 30% reduction in IOP. CONCLUSIONS: MIMS procedure is a relatively simple, short and safe minimally invasive bleb-forming procedure. Its efficacy, as found in this short-term evaluation, lends it suitable for mild and moderate uncontrolled open-angle glaucoma patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04503590 2019-05-29.

Differential Effects of Benzalkonium Chloride on Human Trabecular Meshwork Cells Not Treated or Treated with Transforming Growth Factor-ß2 or Dexamethasone.

Purpose: The objective of the present study was to evaluate the effects of low concentrations of benzalkonium chloride (BAC) (10-7%, 10-6%, or 10-5%) on healthy and glaucomatous human trabecular meshwork (HTM) cells. For this purpose, we used in vitro models replicating a healthy HTM and HTM with primary open-angle glaucoma (POAG) or steroid-induced glaucoma (SG) using two-dimensional (2D) cultures of HTM cells not treated or treated with a 5 ng/mL solution of transforming growth factor-ß2 or 250 nM dexamethasone (DEX). Methods: Analyses were carried out for (1) the intercellular affinity function of 2D HTM monolayers, as determined by transepithelial electrical resistance (TEER) measurements; (2) cell viability; (3) cellular metabolism by using a Seahorse bioanalyzer; and (4) expression of extracellular matrix (ECM) molecules, an ECM modulator, and cell junction-related molecules. Results: In the absence and presence of BAC (10-7% or 10-5%), intercellular affinity function determined by TEER and cellular metabolic activities were significantly and dose dependently affected in both healthy and glaucomatous HTM cells despite the fact that there was no significant decrease in cell viabilities. However, the effects based on TEER values were significantly greater in the healthy HTM. The mRNA expression of several molecules that were tested was not substantially modulated by these concentrations of BAC. Conclusions: The findings reported herein suggest that low concentrations of BAC may have unfavorable adverse effects on cellular metabolic capacity by inducing increases in the intercellular affinity properties of the HTM, but those effects of BAC were different in healthy and glaucomatous HTM cells.

Personality dimensions and treatment adherence among glaucoma patients: the role of self-transcendence.

BACKGROUND: Cloninger's psychobiosocial model of personality proposes that consistent patterns of health behavior are determined by the complex interaction of different neurobiological processes of the patient's temperament and character dimensions. Poor medication adherence is a pervasive problem among glaucoma patients and can lead to increased morbidity and disability. The objective of the present study was to investigate the association between Cloninger's personality dimensions and medication adherence among glaucoma patients. METHODS: The cross-sectional study was conducted among 113 primary open-angle glaucoma (POAG) patients. The treatment adherence was assessed through a valid and reliable self-administered questionnaire, the Culig Adherence Scale (CAS). Personality dimensions were evaluated using the abbreviated version of the Temperament and Character Inventory-Revised (TCI-140). Statistical analyses were performed using TIBCO Statistica 14.0.1. The study protocol was registered in the DRKS - German Clinical Trials Register; (DRKS-ID: DRKS00022081). RESULTS: According to CAS, only 39.8% of patients were adherent to glaucoma treatment. Adherence was significantly negatively related only to the character dimension of Self-Transcendence (p < 0.05). No other TCI-140 dimension was significantly associated with medication adherence (p > 0.05). CONCLUSIONS: The results suggest that POAG patients with higher scores on the Self-Transcendent personality dimension are more likely to experience difficulties adhering to medication regimen. The study highlights the importance of a holistic approach to glaucoma treatment, which takes into account not only the biological aspects of disease but also the psychosocial factors that influence patient behavior. Healthcare providers may need to consider glaucoma patients' personality dimensions, beliefs and values when developing treatment plans and strategies to improve medication adherence.

Prevalence of comorbidities with the potential to increase the risk of nonadherence to topical ocular hypotensive medication in patients with open-angle glaucoma.

OBJECTIVE: To evaluate the prevalence of comorbidities that may limit or prevent adherence to topical ocular hypotensive therapy in patients with open-angle glaucoma (OAG). METHODS: The UK Clinical Practice Research Datalink (CPRD) database of primary and secondary care and prescription records was analyzed to identify patients with a first (index) diagnosis of OAG during 2016-2020. The primary care records of these patients were screened for diagnostic terms linked to prespecified (qualifying) comorbidities considered to have the potential to impact patients' ability to instill eye drops. The prevalence of each of 10 categories of qualifying comorbidity recorded within the period from 5 years before to 2 years after the index OAG diagnosis was analyzed. RESULTS: A total of 100,968 patients with OAG were included in the analysis. Among the patients in the OAG cohort, 13,962 (13.8%) were aged 40-54 years, 32,145 (31.8%) were aged 55-69 years, 42,042 (41.6%) were aged 70-84 years, and 12,819 (12.7%) were aged 85+ years. Within the OAG population, 82.7%, 14.6%, and 2.7% of patients had no category, one category, and two or more categories of qualifying comorbidity, respectively. Qualifying comorbidities were most common in older patients. The most prevalent qualifying comorbidities were categorized as degenerative, traumatic, or pathological central nervous system disorder disrupting cognitive function (5.2%), movement disorder (4.4%), and low vision (4.1%). The prevalence of arthropathies and injuries affecting upper limbs (including arthritis in the hands) was 2.4%. CONCLUSIONS: The presence of comorbidities should be considered when determining whether eye drops are suitable treatment for glaucoma. Neurodegenerative disease affecting cognition and memory, motor disease, and low vision are common comorbidities that may impact adherence to eye drops, and affected patients may benefit from non-drop treatment modalities.

Effectiveness and safety of XEN63 in patients with primary-open-angle glaucoma.

This paper evaluates the effectiveness and safety of XEN63 stent, either standalone or in combination with phacoemulsification, in patients with primary open-angle glaucoma (POAG). Eighty eyes from 80 patients with medically uncontrolled POAG were assigned to undergo XEN63 implant. The primary outcome was the surgical success, defined as an intraocular pressure (IOP) lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 18 mmHg, with or without antiglaucoma medications. Forty-three (53.7%) eyes underwent XEN63-standalone and 37(46.2%) eyes a XEN63 + Phacoemulsification procedure. Success rate was 68.8% (55/80) eyes in the overall study sample, 69.8% (30/43) eyes in the XEN63-standalone group; and 67.6% (25/37) eyes in the XEN63 + Phaco group (p = 0.6133). Preoperative IOP was significantly lowered from 22.1 ± 4.9 mmHg and 19.8 ± 3.7 mmHg to 14.7 ± 5.3 mmHg and 13.8 ± 3.4 mmHg in the XEN63-standalone and XEN63 + Phaco groups, respectively (p < 0.0001 each, respectively); without significant differences between them at any of the time-points measured. Preoperative number of ocular-hypotensive drugs was significantly reduced from 2.3 ± 0.8 to 0.3 ± 0.7 drugs, from 2.5 ± 0.7 to 0.3 ± 0.7 drugs; and from 2.0 ± 0.8 to 0.3 ± 0.7 drugs, in the overall, XEN63-standalone, and XEN63 + Phaco groups, respectively. Regarding safety, 3(42.5%) eyes had transient hypotony at some point during the study, although only in one (1.2%) eye was clinically significant. Four (5.0%) eyes underwent a needling, 4 (5.0%) eyes underwent surgical-bleb-revision, 1 (1.2%) eye required a device replacement and 1 (1.2%) eye a device removal due to maculopathy. XEN63, either alone or in combination with phacoemulsification, significantly lowered IOP and reduced the number of ocular hypotensive medications. The rate of ocular hypotony was relatively high, although it was clinically relevant only in one eye.

How glaucoma patients balance between the advantages and disadvantages of acceptance to the recommended treatment regimen in real-life: Perspectives from a middle-income country.

PURPOSE: Patients with primary open-angle glaucoma (POAG) are required to take long-term treatments with topical medications to halt disease progression. This cross-sectional survey aimed to describe the level of acceptance of Brazilian patients toward the long-term treatment with eyedrops and to find possible correlates of high acceptance. METHODS: POAG patients were recruited from the Glaucoma Service-Santa Casa of Sao Paulo, Sao Paulo, Brazil. Clinical and demographic data were retrieved from participants' electronic records. All patients answered the ACCEPT© questionnaire. This is a generic patient-reported outcome questionnaire specifically developed to assess patients' acceptance of long-term medications and not adherence. Summed scores and those for each domain were calculated to range from 0 to 100 with a higher score indicating greater acceptance. RESULTS: The sample comprised 96 patients with POAG. The mean age was 63.2 ± 8.9 years; 48 were male and 48 female; 55 (57.3%) were white, 36 (37.5%) African-Brazilian, and 5 (5.2%) were of mixed color; most patients (97.9%) had less than high school degree and all had a family income

Prostaglandin-Induced Macular Hole: A Brief Report.

This case series reports on two patients who developed macular holes while on prostaglandin analogs (PGA) therapy. The first case involves a 63-year-old woman with a history of a macular hole of the left eye that had spontaneously closed. After starting PGA therapy for elevated intraocular pressure, cystoid macular edema formed, which resulted in reopening of the macular hole. The second case involves a 64-year-old man with primary open-angle glaucoma, on PGA therapy, with a newly diagnosed small macular hole of the right eye that closed after cessation of the PGA therapy. These cases demonstrate an association between prostaglandin analogs and the formation or reopening of full-thickness macular holes. [Ophthalmic Surg Lasers Imaging Retina 2024;55:112-115.].

Genistein stimulates the viability and prevents myofibroblastic transformation in human trabecular meshwork cells stimulated by TGF-ß.

Primary open-angle glaucoma (POAG) is the most common type of glaucoma leading to blindness. The search for ways to prevent/treat this entity is one of the main challenges of today's ophthalmology. One of such solution seems to be biologically active substances of natural origin, such as genistein (GEN), which can affect the function of isolated trabecular meshwork by the inhibition of protein tyrosine kinase. However, the role of GEN in viability as well as myofibroblastic transformation in human trabecular meshwork cells stimulated by TGF-ß is unknown. Using human trabecular meshwork cells (HTMCs) we investigated the effect of genistein on cell viability and myofibroblastic transformation stimulated by TGF-ß1 and TGF-ß2. Using Real-Time PCR, western blot and immunofluorescence we determined the effect on the expression changes of αSMA, TIMP1, collagen 1 and 3 at mRNA and protein level. We found that genistein increases the viability of HTMCs (1, 2, 3 µg/ml; P < 0.05 and 4, 5, 10, 15, 20 µg/ml; P < 0.01). Moreover, we found that addition of 10, 15 and 20 µg/ml is able to prevent myofibroblastic transformation of HTMCs by decreasing αSMA, TIMP1, collagen 1 and 3 mRNA and protein expression (P < 0.01). Based on the obtained results, we can conclude that genistein is a potential factor that can prevent the myofibroblastic transformation of HTMCs accompanying glaucoma. Describing GEN influence on myofibroblastic transformation processes in HTMC allows us to conclude that it can be considered a potential therapeutic agent or a substance supporting treatment in patients with glaucoma.

Efficacy of Morning Versus Evening Latanoprost/Timolol Fixed Combination for Open-Angle Glaucoma and Ocular Hypertension: A Randomized Clinical Trial.

Purpose: To compare the efficacy of morning and evening latanoprost/timolol fixed-combination (LTFC) dosing in patients with primary open-angle glaucoma (POAG) and ocular hypertension. Methods: In this double-blind, randomized clinical trial, 63 untreated Chinese patients with POAG and ocular hypertension were enrolled. All patients received LTFC and were randomized (1:1) to group 1, morning (8 AM) dosing, or group 2, evening (8 PM) dosing. Vehicle drops were used in the morning or evening, accordingly, to preserve masking. Patients were treated for 4 weeks. Outcomes included mean reduction of the 24-hour intraocular pressure (IOP) and IOP fluctuation from baseline after a 4-week treatment. Results: Fifty-six patients were included in the final analysis. In both groups, the posttreatment IOP values were significantly lower than those at baseline at each 24-hour measuring time point. A significant difference between the groups in IOP reduction from baseline was observed at the 9:30 AM time point (4.01 ± 2.62 vs. 2.42 ± 3.23 mm Hg, evening dosing versus morning dosing group; P = 0.048). Both groups showed decreased IOP fluctuation after treatment. However, the morning dosing group had a significantly greater decrease in diurnal IOP fluctuation than that of the evening dosing group (2.04 ± 2.32 mm Hg vs. 0.50 ± 1.70 mm Hg, respectively; P = 0.012). Conclusions: Both morning and evening LTFC dosing can effectively reduce 24-hour IOP and IOP fluctuation. Morning dosing is more likely to effectively control diurnal IOP fluctuations. Translational Relevance: This multicenter, double-blind, randomized clinical trial generates robust evidence on the optimal LTFC dosing regimen to help clinical decision-making in the treatment of raised IOP.

Outcome of combined trabeculectomy with cataract surgery in patients on prostaglandin analogs and aqueous suppressants.

PURPOSE: To compare the effect of prostaglandin analogs (PGA) against other glaucoma medications (non-PGA) on the intraocular pressure (IOP) outcomes of combined trabeculectomy with phacoemulsification, and the conjunctival cell profile in persons with primary open-angle (POAG) and pseudoexfoliation glaucoma (PXFG). METHODS: A prospective cohort study was conducted among 116 patients with POAG or PXFG on glaucoma medications for a minimum of 3 months undergoing glaucoma triple procedure. Patients were divided into two groups (PGA and non-PGA) based on preoperative exposure to PGA. IOP outcomes were assessed for up to 2 years. Conjunctival biopsy specimens were obtained at the time of surgery, and histopathological analysis was performed. RESULTS: Forty-two patients were in the PGA group, 67 were in the non-PGA group, and seven were lost to follow-up. The non-PGA group had lesser mean postoperative IOP and needed fewer postoperative medications compared to the PGA group in all visits up to 2 years. The non-PGA group had better complete success rate (50.7% vs. 14.3%, P < 0.001). Kaplan-Meier survival estimates showed a significant difference in cumulative complete success rate between non-PGA (67%) and PGA (26%) by 24 months ( P < 0.001). The Cox proportional model showed the type of drug to be significantly associated with surgical failure. Histopathological analysis revealed that the PGA group had higher numbers for each type of inflammatory cell (except mast cells) compared to the non-PGA group. CONCLUSION: Patients on PGA are likely to have a higher postoperative IOP and may need more medications for IOP control after a glaucoma triple procedure.

Evaluation of the LDN-0060609 PERK Inhibitor as a Selective Treatment for Primary Open-Angle Glaucoma: An In Vitro Study on Human Retinal Astrocytes.

The term glaucoma encompasses various neurodegenerative eye disorders, among which the most common is primary open-angle glaucoma (POAG). Recently, the essential role of human retinal astrocytes (HRA) in glaucoma progression has been placed in the spotlight. It has been found that placing the endoplasmic reticulum (ER) under stress and activating PERK leads to apoptosis of HRA cells, which inhibits their neuroprotective effect in the course of glaucoma. Therefore, the aim of the present study was to evaluate the effectiveness of the small-molecule PERK inhibitor LDN-0060609 in countering ER stress conditions induced in HRA cells in vitro. The activity of LDN-0060609 was studied in terms of protein and mRNA expression, cytotoxicity, genotoxicity, caspase-3 level and cell cycle progression. LDN-0060609 at 25 µM proved to be a potent inhibitor of the major PERK substrate, p-eIF2α (49% inhibition). The compound markedly decreased the expression of pro-apoptotic ER stress-related genes (ATF4, DDIT3, BAX and Bcl-2). Treatment with LDN-0060609 significantly increased cell viability, decreased genotoxicity and caspase-3 levels, and restored cell cycle distribution in HRA cells with activated ER stress conditions. These findings indicate that the small-molecule PERK inhibitor LDN-0060609 can potentially be developed into a novel anti-glaucoma agent.

Prescription of glucagon-like peptide 1 agonists and risk of subsequent open-angle glaucoma in individuals with type 2 diabetes mellitus.

Background: The glucagon-like peptide 1 receptor agonist (GLP-1RA) is an antidiabetic medication with vascular protection and anti-inflammatory properties. Theoretically, the use of GLP-1RA should inhibit the development of open-angle glaucoma (OAG) as both vascular damage and inflammation are associated with OAG. Therefore, our objective was to investigate the association between the application of GLP-1RA and the subsequent OAG in individuals with type 2 diabetes mellitus (T2DM). Methods: We conducted a retrospective cohort study by using data from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T2DM were divided into those who used GLP-1RA and those who did not, forming the GLP-1RA and control groups. The primary outcome was the occurrence of OAG based on diagnostic codes. Cox proportional hazard regression was employed to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for OAG. Results: 91 patients in the control group developed OAG, and 40 patients in the GLP-1RA group developed OAG. After adjustment for all covariates, the GLP-1RA group exhibited a significantly lower incidence of OAG compared with the control group (aHR: 0.712, 95% CI: 0.533-0.936. P = 0.0025). In the subgroup analyses, the association between GLP-1RA use and OAG incidence was more pronounced in patients with T2DM using GLP-1RA and aged younger than 60 years (P = 0.0438). Conclusion: The prescription of GLP-1RA is associated with a lower incidence of subsequent OAG in individuals with T2DM, and this association was more significant in patients with T2DM under the age of 60 years.

Human experience and efficacy of omidenepag isopropyl (Eybelis®; Omlonti®): Discovery to approval of the novel non-prostaglandin EP2-receptor-selective agonist ocular hypotensive drug.

More than 75 million people worldwide suffer from ocular hypertension (OHT)-associated retinal and optic nerve degenerative diseases that cause visual impairment and can lead to blindness. In an effort to find novel pharmaceutical therapeutics to combat OHT with reduced side-effect potential, several emerging drug candidates have advanced to human proof-of-concept in recent years. One such compound is a nonprostaglandin (non-PG) EP2-receptor-selective agonist (omidenepag isopropyl ester). Omidenepag (OMD; free acid form) is a novel non-PG that selectively binds to and activates the human EP2-prostglandin receptor (EP2R) with a high affinity (Ki = 3.6 nM) and which potently generates intracellular cAMP in living cells (EC50 = 3.9-8.3 nM). OMD significantly downregulated COL12A1 and COL13A1 mRNAs in human trabecular meshwork (TM) cells, a tissue involved in the pathogenesis of OHT. Omidenepag isopropyl (OMDI) potently and efficaciously lowered intraocular pressure (IOP) in ocular normotensive rabbits, dogs, and monkeys, and also in ocular hypertension (OHT) Cynomolgus monkeys, after a single topical ocular (t.o.) instillation at doses of 0.0001-0.01%. No reduction in IOP-lowering response to OMDI was observed after repeated t.o. dosing with OMDI in dogs and monkeys. Additive IOP reduction to OMDI was noted with brinzolamide, timolol, and brimonidine in rabbits and monkeys. OMDI 0.002% t.o. decreased IOP by stimulating the conventional (TM) and uveoscleral (UVSC) outflow of aqueous humor (AQH) in OHT monkeys. In a Phase-III clinical investigation, 0.002% OMDI (once daily t.o.) reduced IOP by 5-6 mmHg in OHT/primary open-angle glaucoma (POAG) patients (22-34 mmHg baseline IOPs) that was maintained over 12-months. In an additional month-long clinical study, 0.002% OMDI induced IOP-lowering equivalent to that of latanoprost (0.005%), a prostanoid FP-receptor agonist, thus OMDI was noninferior to latanoprost. Additive IOPreduction was also noted in OHT/OAG patients when OMDI (0.002%, once daily t.o.) and timolol (0.05%, twice daily t.o.) were administered. Patients with OHT/POAG who were low responders or nonresponders to latanoprost (0.005%, q.d.; t.o.) experienced significant IOP-lowering (additional approximately 3 mmHg) when they were switched over to OMDI 0.002% (q.d.; t.o.). No systemic or ocular adverse reactions (e.g. iris color changes/deepening of the upper eyelid sulcus/abnormal eyelash growth) were noted after a year-long, once-daily t.o. dosing with 0.002 % OMDI in OHT/POAG patients. However, OMDI caused transient conjunctival hyperemia. These characteristics of OMDI render it a suitable new medication for treating OHT and various types of glaucoma, especially where elevated IOP is implicated.

The association between glaucoma treatment adherence with disease progression and loss to follow-up.

Prospective cohort study from Brazil to evaluate glaucoma treatment adherence using a medication event monitoring system (MEMS) device and correlate with glaucoma progression and loss to follow-up (LTF) after one year of follow up. We included primary open glaucoma (POAG) patients treated with at least one ocular hypotensive eye drop. MEMS devices was used to monitor adherence for 60 days and evaluate the percentage of doses prescribed taken within the 60-day period. We classified patients according to rates of adherence: low adherence (less than 75% from MEMS measurements) and high adherence (more than 75% from MEMS measurements). We applied a questionnaire to investigated self-reported behavior towards treatment behaviors (glaucoma treatment compliance assessment tool, GTCAT). We also correlated rates of treatment adherence with clinical, demographical variables and the occurrence of glaucoma progression or LTF after one year of observation. We included 110 POAG patients and found that 28.18% of them were considered low adherent. We identify several variables associated with poor adherence such as glaucoma progression, LTF, younger age, low educational and income levels, absence of health insurance, years of disease and peak intraocular pressure. Several constructs from the self-reported GTCAT were also correlated with the rates of treatment adherence. To date, this is the first study in Latin America to evaluate glaucoma treatment adherence with MEMS devices and correlate adherence rates with glaucoma progression and LTF. We found a low-adherence rate of 28.18% and several additional risk factors were statistically associated with poor adherence.

Biotissue stent for supraciliary outflow in open-angle glaucoma patients: surgical procedure and first clinical results of an aqueous drainage biostent.

BACKGROUND/AIMS: To report a first-in-human trial in open-angle glaucoma (OAG) subjects treated with a new microinterventional biostent-reinforced cyclodialysis technique to enhance supraciliary aqueous drainage. METHODS: Subjects (N=10; 74.1±7.9 years old) with OAG and cataracts underwent combined phacoemulsification cataract surgery with implantation of a permanent endoscleral supraciliary biostent to reinforce a controlled cyclodialysis cleft. The biostent comprised decellularised scleral allograft tissue microtrephined into a polymer tubular implant intraoperative/postoperative safety, intraocular pressure (IOP) and glaucoma medications were tracked through 12 months postimplantation. RESULTS: Baseline medicated IOP averaged 24.2±6.9 mm Hg with subjects using 1.3±0.8 IOP-lowering medications. Successful biostent implantation was achieved in all individuals without significant complications. Immediate IOP lowering was sustained through 1 year. Twelve-month mean IOP was reduced 40% from baseline to 14.6±3.2 mm Hg (p=0.004; paired two-tailed t-test), and 80% of patients achieved >20% IOP reduction. Biostenting reduced glaucoma medication use 62%, from a baseline mean of 1.3 required medications to 0.5 medications (p=0.037) at postoperative 12 months. The biotissue implant was well tolerated and demonstrated good endothelial safety with only 11% endothelial cell loss at 12 months after combined phaco-biostenting surgery, similar to that expected after phacoemulsification alone. Mean BCVA increased from baseline 20/130 Snellen to 20/36 at postoperative 12 months (p=0.001). CONCLUSION: Supraciliary biostenting in OAG patients is well tolerated, has a good safety profile and produces long-term IOP-lowering while reducing glaucoma medication requirements.

Prescription trends for preservative free glaucoma medication in a public health system.

PURPOSE: To analyze the prescribing trends over a 7-years period, between 2013 and 2020, in a tertiary hospital (Hospital Clinico San Carlos, Madrid, Spain) and its health area. MATERIAL AND METHODS: A retrospective study on the data collected from the information systems, "farm@web" and "Farmadrid", of glaucoma prescriptions in the framework of a public health system (Spanish National Health System) during the last seven years. RESULTS: Prostaglandin analogues were the most commonly used drugs in monotherapy during the study period (range: 36.82% - 47.07%). Fixed combinations of topical hypotensives had an upward trend since 2013 (range: 39.99% - 54.21%), becoming the most dispensed drugs in 2020 (48.99%). Preservative-free eye drops (lacking benzalkonium chloride, BAK) have displaced preservative containing topical treatments in all pharmacological groups. In 2013, BAK-preserved eye drops accounted for 91.1% of the total prescriptions, however in 2020 they only accounted for 34.2% of total prescriptions. CONCLUSIONS: The results of the present study highlight the current trend to avoid BAK-preserved eye drops for the treatment of glaucoma.

Association of Postural Blood Pressure Response With Disease Severity in Primary Open Angle Glaucoma.

PRCIS: Patients with primary open angle glaucoma (POAG) demonstrated exaggerated postural blood pressure dip in recumbency that was positively correlated with the severity of glaucomatous optic neuropathy (GON). Postural dip testing can be used clinically as a marker of systemic vascular dysregulation in GON risk assessment. OBJECTIVE: To investigate whether patients with POAG demonstrated abnormal postural blood pressure response to recumbency and whether such abnormal postural response correlated with GON severity. PATIENTS AND METHODS: This is a prospective observational study where 47 patients with POAG underwent intraocular pressure and systemic arterial blood pressure, systolic blood pressure (SBP) and diastolic blood pressure (DBP), measurement in seated and after 20-minute recumbency positions. Mean arterial blood pressure (MABP) was calculated for seated and recumbent positions. The percentage difference between seated and recumbent SBP, DBP, and MABP was calculated according to which participants were divided into 3 groups, that is, nondippers, normal dippers, and exaggerated dippers with percentage dips of <10%, ≥10%≤20%, >20%, respectively. Participants underwent optical coherence tomography of optic nerve head to measure retinal nerve fiber layer thickness (RNFLT) which was used as a structural biomarker of GON. RESULTS: RNFLT was lower in exaggerated dippers than in nondippers and normal dippers. There was a negative correlation between postural dip and average RNFLT. Linear regression showed that postural dip was associated with lower RNFLT independent of age and intraocular pressure. The χ 2 independence test demonstrated a strong relation among corresponding dip groups for SBP, DBP, and MABP. However, it showed no significant relation between hypertension and postural dip. Fisher exact test showed no relation between antihypertensive medication and postural dip. CONCLUSIONS: Patients with POAG demonstrated abnormal postural blood pressure response comprising exaggerated recumbent dip which was positively correlated with disease severity. Postural dip assessment may serve as a simple clinic-based test of systemic vascular dysregulation as part of GON risk evaluation.

Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension.

PURPOSE: A randomized, double-masked, multicenter, phase 2 trial to evaluate the long-term safety and efficacy of travoprost intraocular implant, an extended-release drug delivery system designed to provide uninterrupted sustained intraocular pressure (IOP)-lowering therapy, thereby reducing patient treatment burden and improving adherence with IOP-lowering medication. METHODS: Patients with open-angle glaucoma or ocular hypertension were administered a fast-eluting implant (FE implant, n = 51) and received twice-daily (BID) placebo eye drops, a slow-eluting (SE implant, n = 54) and received BID placebo eye drops, or underwent a sham surgical procedure and received BID timolol 0.5% (n = 49). IOP was measured at baseline, day 1-2, day 10, week 4, week 6, month 3, and every 3 months thereafter through 36 months. Efficacy was evaluated by mean change from 8:00 AM unmedicated baseline IOP through month 36, and the percentage of patients receiving the same or fewer topical IOP-lowering medications as at screening (pre-study). Safety was evaluated by adverse events and ophthalmic parameters. RESULTS: Clinically and statistically relevant IOP-lowering treatment effects were observed through month 36 after a single administration of the travoprost implant compared with BID timolol with mean IOP reductions ranging from 7.6 to 8.8 mmHg for the FE implant group, from 7.3 to 8.0 mmHg for the SE implant group, and from 7.3 to 7.9 for the timolol group at the 8:00 AM timepoint (P < 0.0001 for all treatment groups at all visits). At months 12, 24, and 36, a greater percentage of FE and SE implant patients versus timolol patients were well controlled on the same or fewer topical IOP-lowering medications compared with screening with 63 and 69% for the FE and SE implants groups, respectively, versus 45% for the timolol group at month 36. The safety profile of the implant was favorable; there were no dislodgements, no explantations, no adverse events of conjunctival hyperemia or periorbital fat atrophy, no discontinuations due to study eye adverse events, nor any serious adverse events in the study eye. Comparable changes from baseline in corneal endothelial cell counts were observed in the three treatment groups over the 36 months. CONCLUSION: The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile. The travoprost intraocular implant promises to be a meaningful addition to the interventional glaucoma armamentarium by addressing the key shortcomings of topical IOP-lowering medications, including low adherence and topical side effects while controlling IOP for up to 36 months. TRIAL REGISTRY: ClinicalTrials.gov identifier NCT02754596 registered 28 April 2016.

Appropriate patient population for future visual system axon regeneration therapies.

A number of blinding diseases caused by damage to the optic nerve result in progressive vision loss or loss of visual acuity. Secondary glaucoma results from traumatic injuries, pseudoexfoliation or pigmentary dispersion syndrome. Progressive peripheral vision loss is common to all secondary glaucoma irrespective of the initial event. Axon regeneration is a potential therapeutic avenue to restore lost vision in these patients. In contrast to the usual approach of having the worst possible patient population for initial therapies, axon regeneration may require consideration of appropriate patient population even for initial treatment trials. The current state of axon regeneration therapies, their potential future and suitable patient population when ready is discussed in this perspective. The selection of patients are important for adoption of axon regeneration specifically in the areas of central nervous system regenerative medicine. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Biomedical Engineering Metabolic Diseases > Molecular and Cellular Physiology.