Medical Treatment Of Glaucoma Research Articles

Effect of Repeated Intravitreal Injections in Glaucoma Spectrum Diseases.

To evaluate whether repeated intravitreal injections (IVI) with an anti-vascular endothelial growth factor (anti-VEGF) agent are associated with glaucomatous progression in eyes with glaucoma spectrum diseases (GSD). Single-center, retrospective, longitudinal study of patients with bilateral and similar GSD who: (1) received ≥8 IVI in only one eye during the study period; (2) had ≥2 retinal nerve fiber layer thickness (RNFL) measurements obtained by spectral-domain optical coherence tomography (SD-OCT) at least 12 months apart. The primary outcome was the absolute RNFL thickness change, comparing injected and fellow uninjected eyes. Linear mixed effects models were constructed, including a multivariable model. Sixty-eight eyes from 34 patients were included, 34 injected and 34 fellow uninjected eyes. Average baseline age was 67.68±21.77 years with a follow-up of 3.66±1.89 years and 25.12±14.49 IVI. RNFL thickness decreased significantly from 80.92±15.78 to 77.20±17.35 μm (p<0.001; -1.18±1.93 μm/year) in injected eyes and from 79.95±17.91 to 76.61±17.97 μm (p<0.001; -1.07±0.98 μm/year) in uninjected eyes. In a multivariable linear mixed model of injected eyes, only higher baseline RNFL thickness (p < 0.001) significantly predicted higher absolute RNFL thickness loss. Neither absolute RNFL thickness variation (p=0.716) nor RNFL rate (p=0.779) was significantly different between paired injected and uninjected eyes. Absolute IOP variation was not significantly different between groups (16.62±4.77 to 15.09±4.34 mmHg in injected eyes and 17.68±5.01 to 14.50±3.39 mmHg in fellow uninjected eyes; p=0.248). The proportion of eyes receiving glaucoma medical treatment increased significantly in both groups (55.9% to 76.5% in injected eyes; p=0.039; 58.8% to 76.5% in uninjected eyes; p = 0.031). The number of glaucoma medications also increased significantly in both groups (1.03±1.11 to 1.59±1.18 glaucoma medications in injected eyes; p=0.003; 1.09±1.11 to 1.56±1.19 glaucoma medications in uninjected eyes; p=0.003). Repeated IVI do not seem to accelerate glaucomatous progression. Future studies with a longer follow-up are needed.

Factors influencing the effectiveness of trabeculectomy: following materials of the City Multidisciplinary Hospital No. 2

BACKGROUND: Despite the ever-expanding arsenal of IOP-lowering surgeries, trabeculectomy remains the most common procedure amongst them. Therefore, the identification of factors reducing its effectiveness and potentially being able to change the surgical treatment plan is of particular importance.&#x0D; AIM: To identify factors reducing trabeculectomy effectiveness.&#x0D; MATERIALS AND METHODS: The study group consisted of 443 consecutively enrolled patients who were operated in 20162020 in Saint Petersburg City Multidisciplinary Hospital No. 2 for primary open-angle decompensated glaucoma and then observed for 6 to 24 months. Using statistical research methods, factors that significantly affected the impact of the procedure were identified.&#x0D; RESULTS: The main predictors of trabeculectomy failure following the order of decreasing importance of established relations (p) were: loss of effectiveness of the preceding IOP-lowering procedure (р = 0.0001), dry eye syndrome (р = 0.013), number of drop instillations per day (р = 0.041), and excessive preservative load due to unnecessarily aggressive topical glaucoma treatment (р = 0.039). An obvious demonstration of excessive therapy is a simultaneous administration of four IOP-lowering medications. It also causes scarring of the procedure area, especially in patients previously operated for glaucoma. Null preservative load and prostaglandin monotherapy are associated with guaranteed complete success of trabeculectomy. Unlike the intensity of medical glaucoma treatment, its duration does not have such a significant impact on trabeculectomy outcomes (р = 0.270). Close to a significant one is the relationship between poor surgical outcomes and advanced stages of the disease (р = 0.052).&#x0D; CONCLUSIONS: The main factors affecting the effectiveness of trabeculectomy were failure of the previous IOP-lowering surgeries; concomitant dry eye syndrome, arising or being aggravated by unduly intense and prolonged pharmacological effects on the eye surface; as well as delayed appliance for surgical IOP normalization at advanced disease stages.

When Diabetes Interferes with Medical Treatment of Glaucoma in Ocular Surface Involvement

Glaucoma is a common blinding disease. Many of the currently available hypotonating eye drops are associated with adverse effects, such as ocular surface damage, which sometimes lead to discontinuation of treatment. We report the case of a 60-year-old man with glaucoma under hypotonizing treatment and unbalanced diabetes with diabetic retinopathy and diabetic peripheral neuropathy. The patient presented a severe damage of the ocular surface most probably shared between two components; the antiglaucoma treatment and their conservative on the one hand and the badly balanced diabetes with neuropathy on the other hand.

ROCK inhibitors in glaucoma medical treatment

AbstractRho kinase inhibitors are a novel advancement in glaucoma medical treatment and have been recently approved for instruction in the market in fixed combination with the prostaglandin analogue Latanoprost. They have a novel mechanism of action based on their ability to improve humour aqueous outflow through the conventional trabecular meshwork pathway.Rho family proteins are GTPases that localize in the intracellular side of plasma membrane and are activated by several plasma membrane signal receptors, including TGF‐β and hormones.Activated Rho then activates Rho‐associated protein kinases which further transmit the stimulus to downstream effectors. The whole pathway is involved in several cellular activities, including actin cytoskeleton organization, cell adhesion and motility, proliferation and apoptosis, and remodelling of the ECM. ROCKs mediate pro‐fibrotic processes in many tissues and pathological conditions. In cultured human TM cells, exposure to a ROCK inhibitor caused retraction and rounding of cell bodies, as well as disruption of actin bundles and impaired focal adhesion formation. ROCKs have been associated when administered topically to a reduction in episcleral venous pressure that might contribute to their ocular hypotensive effects.MERCURY‐3, was a prospective, randomized, double‐masked, active‐controlled study to assess the efficacy, safety, and tolerability of the ROCK inhibitor netarsudil 0.02% in fixed combination with latanoprost 0.005% compared with the fixed combination of bimatoprost 0.03%/timolol 0.5%.The results of the study showed non inferiority of the netarsudil fixed combination despite a slightly worse local tolerability profile.Current management approaches aim to reduce IOP but do not tackle the principal site of increased outflow resistance that is the TM. ROCK inhibition shows for the first time the ability for directly modulating the TM permeability and represents a new clinical treatment for glaucoma.

Role of antioxidants in glaucoma medical treatment

AbstractGlaucoma is a neurodegenerative disease characterized by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. This presentation intends to update the knowledge about oxidative stress mechanisms in relation with glaucoma and the effect of antioxidant coadjuvant therapy on this disease.

Intraocular injections of glaucoma medications

AbstractThe injection of slow release antiglaucoma drugs could be an alternative in order to guarantee the adherence to glaucoma medical treatment and to reduce the rate of progression.There are multiple possibilities. In this moments, only slow release bimatoprost injection in anterior chamber has been approved by FDA. The hypotensive effect could be maintained for 6 months. Similar studies with sustained release of another prostaglandine analogs, like latanoprost and travoprost, are undergoing.Another option is the iDose containing travoprost that is implanted in the trabecular meshwork. A phase III study is undergone.Another possibility under investigation is supraciliary, subconjunctival, intravitreous and intrascleral injection of different active products.In the next future, the injection of antiglaucoma drugs could have an important role in glaucoma medical treatment.

Clinical applications of molecular genetics research in glaucoma daily practice

AbstractPersonalized medicine using genetic information to predict disease development and tailor preventive interventions is an evolving field. In the last decade, molecular genetic studies in glaucoma have experienced a great advance, partly due to the appearance of new diagnostic technologies such as high‐efficiency and rapid next‐generation sequencing (NGS) that allows the sequencing of gene panels in a short time, exomes or complete genomes. With these advances, the list of candidate genes associated with the diagnosis of POAG has greatly increased and there is increasing information about the molecular mechanisms underlying POAG. The new genes involved in the pathology of glaucoma are mainly related to oxidative stress, DNA repair mechanisms, mitochondrial DNA, sex hormones, etc. The study of loci associated with quantitative endophenotypic traits has also been proposed that would act as risk factors for the disease (pachymetry, axial length, anterior chamber depth, diameter of the retinal vessels, papillary excavation, etc.) that, when added together, would increase the risk of developing POAG.On the other hand, exome sequencing can be useful for the detection of polymorphisms in genes associated with the individual response to medical treatment of glaucoma (pharmacogenic bases of glaucoma) and the possible success of filtering surgery in these patients (genetic bases of glaucoma). Early fibrosis in individuals with glaucoma.Recent studies have described the existence of polymorphisms against the ocular pharmacological receptors of the drugs commonly used to treat glaucoma that would cause an absence of pharmacological response. These would be polymorphisms in genes encoding drug receptors for prostaglandin analogs (rs3766355; rs3753380) and topical beta‐blockers (rs1042714) and would provide valuable information on whether the patient will respond well to these drugs or will be resistant them and thus plan their antiglaucomatous treatment in a personalized and early manner. The main cause of surgical failure in patients with glaucoma is fibrosis of the conjunctival bleb. This may be due to acquired factors (prolonged use of topical medication causing inflammation of the ocular surface, eye drops with preservatives, dry eye, etc.), or genetic factors that would cause individual susceptibility to early fibrosis of the conjunctival bleb. In recent years, genes that present an overexpression at the conjunctival level in cases of early surgical failure have been described and studies have also been published on the existence of systemic and genetic humoral factors responsible for an individual hyperfibrosing genetic profile. Definitely. the study of exomes by means of NGS would allow us to quickly and effectively discover different aspects of the glaucomatous pathology of our patients: molecular diagnosis, detection of asymptomatic relatives, genetic counselling, type of appropriate hypotensive treatment and type of surgical technique that would increase surgical success. And so in the near future we will be able to personalize and administer early treatment that is key to stopping the destruction of the optic nerve in these patients.

Glaucoma medical treatment as a predictor of XEN45 subconjunctival gel implant hypotensive efficacy.

The aim of this study was to determine the preoperative characteristics influencing hypotensive efficacy of the XEN45 gel stent in patients with open-angle glaucoma at one-year follow-up. This was a retrospective multicentre study. All patients who underwent XEN45 gel stent implantation between January 2017 and January 2021 were included. The main study outcome was the assessment of one-year postoperative intraocular pressure (IOP) and glaucoma medication differences according to the number and type of preoperative topical treatments or glaucoma surgery, glaucoma stage and time since diagnosis. Follow-up period was 1-year post-surgery in all cases. IOP reduction and surgery success (not requiring reoperation or pressure failures [IOP > 18mmHg and < 20% reduction in IOP]), safety and cost savings in topical glaucoma therapy after surgery were secondarily assessed. Linear regression analysis to determine the preoperative parameters influence on 1-year postoperative results was performed. XEN45 gel stent was implanted in 85 patients. One-year postoperative mean IOP dropped from 20.6 ± 4.1 to 13.7 ± 2.8mmHg (p < 0.0001). Likewise, mean number of topical treatments decreased from 2.05 ± 0.9 to 0.36 ± 0.65 (p < 0.001). Both were mainly influenced by the number of preoperative glaucoma treatments, such that for each one-glaucoma medication increase, postoperative intraocular pressure increased by 1.18mmHg (95% CI 0.56-1.79, p < 0.0001) and number of glaucoma medications increased by 0.3 (95% CI 0.16-0.43, p < 0.001). Overall success rates (with and without supplemental glaucoma medication use) were 97.6% (95% CI 94.5-100%), 87.1% (95% CI 80.2-87.1%) and 61.2% (95% CI 51.6-72.5%) at 3, 6months and 1year after surgery. No sight-threatening adverse events were reported. Mean annual cost savings on medical treatment since surgery reached EUR 251.19 ± 169. 93 euros. One year after surgery, XEN45 gel implant significantly reduced IOP and number of topical medications with an adequate safety profile being both mainly influenced by the number of preoperative glaucoma treatments.

Assessment of the readability and quality of online patient education materials for the medical treatment of open-angle glaucoma

ObjectivePatient adherence to glaucoma medications is poor, and is linked to low literacy levels. Patients commonly use the internet to access health information, and it is recommended that patient information...

Malignant glaucoma following gonioscopy-assisted transluminal trabeculotomy: a case report

BackgroundTo report a case of malignant glaucoma that developed after gonioscopy-assisted transluminal trabeculotomy (GATT).Case presentationAn 85-year-old male pseudophakic patient affected by pseudoexfoliative glaucoma (PEXG), unresponsive to medical glaucoma treatment, underwent uneventful GATT surgery. On the first day after surgery, the eye showed a shallow central and peripheral anterior chamber (AC) with a raised intraocular pressure (IOP) measured at 55 mmHg. Optical coherence tomography and ultrasound biomicroscopy confirmed the diagnosis of malignant glaucoma.Laser iridotomy, posterior capsulotomy and hyaloidotomy were performed, and the patient was treated with atropine sulphate 1%, maximum topical and systemic ocular hypotensive drugs with no improvement in the IOP. Subsequently, the patient underwent pars plana anterior vitrectomy, resulting in deepening of the AC with opening of the iridocorneal angle and decrease of the IOP. No further postoperative complications were recorded, and the IOP remained controlled 12 months after surgery without antiglaucoma medications.ConclusionsDespite the minimally invasive profile of GATT, malignant glaucoma may develop after this procedure. Early recognition and prompt treatment are mandatory for preventing permanent visual loss.

A Randomized Controlled Clinical Trial to Compare Conventional Drug Instillation to A Device Dropper Method in Medical Treatment of Glaucoma

ABSTRACT Purpose To compare and analyze the performance of a device dropper (DD) over conventional drop instillation (CDI) method on ease of administration, compliance, patient satisfaction, and intraocular pressure (IOP) control in persons with glaucoma on ocular hypotensive medications. Methods We enrolled 72 individuals with primary open-angle glaucoma or ocular hypertension, on treatment with fixed combination (α agonist+β blocker) drugs for at least 6 months. These were randomized into two groups (36 in each arm). Group 1 administered the drug with a DD and Group 2 used CDI method. Recruited individuals were interviewed for subjective difficulties using a formatted questionnaire at first month follow-up and IOP change from baseline was evaluated. Results Baseline demographic and ocular characteristics were similar in both groups. 57.1% in the conventional instillation and none in the DD had reported difficulty in using the eye drops on follow-up visit. DD group had significantly less spillage and contamination of eye surface or dropper tips, required minimal assistance, accurately targeted on first drop placement directly into the eye compared to CDI group (p-value<0.001). Mean IOP was comparable between the two groups. Conclusion DD instillation method was observed to be easier to administer, more accurate in targeting the conjunctival cul-de-sac, reduced wastage with lesser contamination compared to the CDI technique. DDs may be expected to have better compliance and effectiveness in medical management of glaucoma.

Medical anti-glaucoma therapy: Beyond the drop.

Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to prescribed anti-glaucoma drop regimens. In an effort to circumvent these challenges, a number of new anti-glaucoma therapies with sustained effects have emerged. Methods for sustained delivery of prostaglandin analogs are being intensely investigated and many are in human clinical trials. Intracameral devices include the following: Allergan's Durysta™ Bimatoprost SR, Envisia Therapeutics' ENV515 travoprost implant, Glaukos' iDose™ , Ocular Therapeutix's OTX-TIC travoprost implant, and Santen's polycaprolactone implant with PGE2-derivative DE-117. Other prostaglandin-based technologies include Allergan's bimatoprost ring (placed in the conjunctival fornix), Ocular Therapeutics' OTX-TP intracanalicular travoprost implant, subconjunctival latanoprost in a liposomal formulation, and the PGE2 derivative PGN 9856-isopropyl ester that is applied to the periorbital skin. Exciting breakthroughs in gene therapy include using viral vectors to correct defective genes such as MYOC or to modulate gonioimplant fibrosis, CRISPR technology to edit MYOC or to alter aquaporin to reduce aqueous humor production, and siRNA technology to silence specific genes. Stem cell technology can repopulate depleted tissues or, in the case of Neurotech's Renexus® NT-501 intravitreal implant, serve as a living drug delivery device that continuously secretes neurotrophic factors. Other unique approaches involve nanotechnology, nasal sprays that deliver drug directly to the optic nerve and noninvasive alternating current stimulation of surviving cells in the optic nerve. Over time these modalities are likely to challenge the preeminent role that drops currently play in the medical treatment of glaucoma in animals.

NIGHTMARES FROM TOPICAL TIMOLOL EYE DROPS: A CASE REPORT

Topical timolol eyedrops are frequently used as medical treatment of glaucoma. They decrease the production of aqueous humor by blocking the beta adrenergic receptors of ciliary body. Although systemic absorption of eyedrops is negligible, still it can cause some serious side effects like bradycardia, heart block, bronchospasm, confusion and hypotension. We present a case who developed nightmares with use of topical beta-blockers. He was a chronic case of primary open angle glaucoma whose target intraocular pressure (IOP) couldn’t be achieved with latanoprost alone, the first line drug, so we put him on topical timolol twice daily dosage to further decrease the IOP. On his follow-up visit he complained about bad dreams since starting timolol eye drops. This case report will add to the list of already known other side effects of timolol usage in glaucoma patients.

Factors Predetermining Increased Aqueous Humour Flare in Long-Term Glaucoma Treatment.

Glaucoma patients often require long-term or even lifelong medical antiglaucomatous treatment. Benzalkonium chloride (BAK) is the most frequently used preservative in medical glaucoma treatment. Laser flare photometry is the noninvasive quantitative measurement of anterior chamber protein level and helps tracking intraocular inflammation. The purpose of our study was to evaluate the ocular aqueous humour flare in glaucoma patients, scheduled for cataract surgery without any other ocular diseases, and the association with pseudoexfoliation (PEX) syndrome, number of medications used, and BAK. A prospective case-control age- and gender-matched study, including open-angle glaucoma patients (>2 years of treatment) with cataract, matched with cataract patients with no other ocular pathology (control group). We found that the aqueous humour flare was higher in the glaucoma group than in the control group. PEX syndrome increased the aqueous humour flare independently from glaucoma diagnosis. The number of used antiglaucomatous medications correlated moderately with the aqueous humour flare. The BAK index showed weak positive correlation with aqueous humour flare. A variety of factors can affect aqueous humour flare increase, including PEX syndrome, medical substance used to treat glaucoma, number of different medications, and presence of BAK. The combination of these factors is of key importance to long-term glaucoma treatment.

Association of preservative‐free versus glaucoma eye drops with preservatives and further glaucoma surgery. A retrospective study based on the French national health insurance information system, 2008‐2016

AbstractPurposePreservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. This study aimed to assess the impact of preservatives on further glaucoma surgery among patients with glaucoma or ocular hypertension in France between 2008 and 2016.MethodsThis was a retrospective analysis of prospectively collected data from a French medical‐administrative database. Three groups were created according to the level of preservative consumption during the whole follow‐up: ‘0% preservatives’, ‘mixed’ and ‘100% preservatives’. The risk of glaucoma surgery was estimated according to preservative exposure indicators in Cox multivariate models. The adjustment variables were age, sex, number of glaucoma drops classes, use of systemic anti‐hypertensive treatment, and duration of exposure to intraocular pressure (IOP)‐lowering agents.ResultsThe sample consisted of 12 454 patients firstly treated for glaucoma or ocular hypertension between January, 1st, 2008 and December, 31st, 2015. The median (interquartile range) follow‐up was 4.1 (1.7–6.1) years. A total of 231 (1.9%) patients underwent glaucoma surgery during follow‐up. On multivariable analysis, the risk of glaucoma surgery was increased for the ‘mixed’ group [hazard ratio (HR) = 3.94 (95% CI, 1.54–10.05)] and for the ‘100% preservative’ group [HR = 7.97 (95% CI, 3.07–20.67)] when compared with the 0% preservatives group.ConclusionsWe found a strong association between exposure to glaucoma eye drops preservatives and the prevalence of further glaucoma surgery. In real life, in a large sample of patients, these results bring new and novel arguments to privilege preservative‐free IOP‐lowering eyedrops for the medical treatment of glaucoma.

ISOPT Clinical Hot Topic Panel Discussion on Glaucoma.

As part of the 14th International Symposium on Ocular and Pharmacological Therapeutics, a unique panel was gathered to discuss two cardinal questions related to the treatment of glaucoma, peeking into the future: (1) What shape and form will glaucoma medical treatment have five and fifteen years from today, and (2) Will personalized medicine be commonly used five years from now. For each of the questions, we assigned an "optimist" and "pessimist" who provided the assigned point of view, for a total of 4 discussants, the authors of this panel discussion.

Glaucoma: a prescriber's guide

Glaucoma is a common eye condition that features progressive optic nerve damage with corresponding visual field loss. According to The Royal College of Ophthalmologists' The Way Forward: Glaucoma Report, it is destined to become an escalating problem due to an increasingly elderly population expected in the next 2 decades. In order to cope with the anticipated demand, hospital eye services are required to re-think the way care is delivered, and it is likely that more multidisciplinary clinical staff will be needed to manage glaucoma patients. Medical treatment with eye drops is sufficient for most patients, with surgery offered to those with worsening glaucoma despite medical and/or laser treatment, or patients who are intolerant to such treatment. This article aims to provide an overview of glaucoma with a focus on the prescribing options available and the associated challenges of the medical treatment of glaucoma.

New classes of glaucoma medical treatment

New classes of glaucoma medical treatment

Brinzolamide/Brimonidine Fixed Combination: Simplifying Glaucoma Treatment Regimens.

IntroductionTo simplify the medical treatment of glaucoma for patients on multiple drops by introducing brinzolamide/brimonidine tartrate fixed combination (BBFC) ophthalmic suspension 1%/0.2% (SIMBRINZA®; Alcon Laboratories, Inc., Fort Worth, TX, USA) to the drop regimen and to establish its efficacy. To demonstrate that fixed combination (FC) therapies are associated with improvements in treatment adherence and persistence with reduced exposure to preservative-related ocular surface problems.MethodsRetrospective study: 76 patients were identified as taking BBFC following a switch in treatment regimen. Intraocular pressure (IOP) prior to and 2–17.5 months (average 5.4 months) after the introduction of BBFC was measured. The change in the average number of bottles used per eye was recorded. The rate of adverse effects (AEs) of BBFC was recorded. A two-tailed paired sample t test was used to compare IOP prior to and after the introduction of BBFC for each eye.ResultsMean change in IOP after BBFC introduction BBFC: − 2.76 mmHg (p < 0.0001). BBFC intolerance: 13%. On average there was a 0.24 reduction in the number of bottles of IOP-lowering medication used per eye (p < 0.0064).ConclusionA switch to BBFC in the drop regimen is associated with a significant drop in IOP with reduced drop burden. Instead of a third IOP-lowering medication and bottle, a practitioner should consider using BBFC + prostaglandin analogue/FC drop for effective IOP control, reduced drop burden, reduced preservative load and increased likelihood of adherence. This study promotes the concept that any treatment should principally be assessed from the patients’ perspective and quality of life.

New Developments in the Medical Treatment of Glaucoma

To focus on new medical therapies that lower intraocular pressure in glaucoma. We summarize new classes of medications to help treat open-angle glaucoma and ocular hypertension, including modified prostaglandin analogues, such as latanoprostene bunod, and prostanoid receptor agonists, ONO-9054 and DE-117. We summarize the differences among the Rho kinase inhibitors that modulate the actin cytoskeleton. We present preclinical and clinical data on the adenosine receptor agonist, trabodenoson, and the RNAi-based compound, bamosiran. Several promising drugs with novel mechanisms of action are in development to lower intraocular pressure in glaucoma. The Food and Drug Administration approved latanoprostene bunod and netasurdil for commercial use in late 2017. These drugs mark the first new compounds to treat glaucoma in over two decades.