Treatment Option For Glaucoma Research Articles

Pronounced synergistic neuroprotective effect of GDNF and CNTF on axotomized retinal ganglion cells in the adult mouse

Neuroprotection is among the potential treatment options for glaucoma and other retinal pathologies characterized by the loss of retinal ganglion cells (RGCs). Here, we examined the impact of a neural stem (NS) cell-based intravitreal co-administration of two neuroprotective factors on the survival of axotomized RGCs. To this aim we used lentiviral vectors to establish clonal NS cell lines ectopically expressing either glial cell line-derived neurotrophic factor (GDNF) or ciliary neurotrophic factor (CNTF). The modified NS cell lines were intravitreally injected either separately or as a 1:1 mixture into adult mice one day after an optic nerve lesion, and the number of surviving RGCs was determined in retinal flat-mounts two, four and eight weeks after the lesion. For the transplantation experiments, we selected a GDNF- and a CNTF-expressing NS cell line that promoted the survival of axotomized RGCs with a similar efficacy. Eight weeks after the lesion, GDNF-treated retinas contained 3.8- and CNTF-treated retinas 3.7-fold more RGCs than control retinas. Of note, the number of surviving RGCs was markedly increased when both factors were administered simultaneously, with 14.3-fold more RGCs than in control retinas eight weeks after the lesion. GDNF and CNTF thus potently and synergistically rescued RGCs from axotomy-induced cell death, indicating that combinatorial neuroprotective approaches represent a promising strategy to effectively promote the survival of RGCs under pathological conditions.

Evolution of Cyclophotocoagulation.

Cyclodestructive techniques have been a treatment option for refractory glaucoma since its first use in the 1930s. Over the past nine decades, cyclodestruction has advanced from the initial cyclodiathermy to micropulse transscleral cyclophotocoagulation (MP-TSCPC) which is the current treatment available. Complications associated with cyclodestruction including pain, hyphema, vision loss, hypotony and phthisis have led ophthalmologists to shy away from these techniques when other glaucoma treatment options are available. Recent studies have shown encouraging clinical results with fewer complications following cyclophotocoagulation, contributing greatly to the current increase in the use of cyclophotocoagulation as primary treatment for glaucoma. We performed our literature search on Google Scholar Database, Pubmed, Web of Sciences and Cochrane Library databases published prior to September 2017 using keywords relevant to cyclodestruction, cyclophotocoagulation and treatment of refractory glaucoma.

Minimally Invasive Modalities for Treatment of Glaucoma: An Update

Purpose of Review: In recent years, Minimally Invasive Glaucoma Surgery (MIGS) and laser-based procedures have been gaining popularity as glaucoma treatment options. As such, they represent active areas of research. This article reviews some of the notable recent and forthcoming developments in this field. Recent Findings: The MIGS devices and cyclophotocoagulation have been focused on achieving satisfactory success rate as either combined with phacoemulsification or standalone procedure. They also have superior safety profile when compared to traditional incisional glaucoma surgeries. In addition to the promising data available thus far, more comprehensive investigations on the long-term efficacy and safety of these interventions are currently underway. Summary: New minimally invasive surgical modalities have shown considerable potential in intraocular pressure (IOP) and the number of post-surgical medications with rare complications. The rising popularity of these devices and procedures may represent a shift in treatment paradigm from medical therapy towards earlier surgical intervention, especially in the treatment of mild-to-moderate glaucoma.

Cyclodialysis: an update.

Cyclodialysis is the result of the separation of the longitudinal ciliary muscle fibers from the scleral spur, which creates an abnormal pathway for aqueous humor drainage that may lead to ocular hypotony. For many years cyclodialysis was considered a treatment option for glaucoma. However, today it usually occurs as a complication of blunt trauma or more rarely as a complication of anterior segment ocular surgery. Ocular hypotony can lead to cataract development, optic disk swelling, refractive changes, and several retinal complications, making accurate identification and timely intervention of the cleft mandatory. Traditionally gonioscopy was the only available technique to diagnose and localize the cleft. However, other tests such as optical coherence tomography, magnetic resonance imaging, transillumination, and specially ultrasound biomicroscopy are now available for the diagnosis of cyclodialysis. Multiple treatment options are alsoavailable for this condition. Although medical treatment can be effective to close small clefts, surgery is needed in most patients to restore ocular pressure.

24-h Efficacy of Glaucoma Treatment Options.

Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0302-0) contains supplementary material, which is available to authorized users.

Nanoparticle cross-linked collagen shields for sustained delivery of pilocarpine hydrochloride

Glaucoma is a common progressive eye disorder which remains the second leading cause of blindness worldwide. Current therapy involves frequent administration of eye drops which often results in poor patient adherence and therapeutic outcomes. The aim of this study was to overcome these limitations by developing a novel nanoparticle cross-linked collagen shield for sustained delivery of pilocarpine hydrochloride (PHCl). Three metal oxide nanoparticles (NPs); titanium dioxide (TiO2), zinc oxide (ZnO) and polyvinylpyrrolidone (PVP) capped zinc oxide (ZnO/PVP), were evaluated for their cytotoxicity as well as shield transparency before selecting ZnO/PVP NPs as the ideal candidate. Cross-linked collagen shields were then characterized for their mechanical strength, swelling capacity and bioadhesive properties, with ZnO/PVP NP cross-linked shields showing the most favorable characteristics compared to plain films. The shield with the best properties was then loaded with PHCl and in vitro release of zinc ions as well as PHCl was measured without and with further cross-linking by ultraviolet irradiation. The concentration of zinc ions released was well below the IC50 rendering them safe for ocular use. Moreover, collagen shields cross-linked with ZnO/PVP NPs released PHCl over a period of 14 days offering a promising sustained release treatment option for glaucoma.

Neuroprotection in the treatment of glaucoma – A focus on connexin43 gap junction channel blockers

Glaucoma is a form of optic neuropathy and a common cause of blindness, affecting over 60 million people worldwide with an expected rise to 80 million by 2020. Successful treatment is challenging due to the various causes of glaucoma, undetectable symptoms at an early stage and inefficient delivery of drugs to the back of the eye. Conventional glaucoma treatments focus on the reduction of elevated intraocular pressure (IOP) using topical eye drops. However, their efficacy is limited to patients who suffer from high IOP glaucoma and do not address the underlying susceptibility of retinal ganglion cells (RGC) to degeneration. Glaucoma is known as a neurodegenerative disease which starts with RGC death and eventually results in damage of the optic nerve. Neuroprotective strategies therefore offer a novel treatment option for glaucoma by not only preventing neuronal loss but also disease progression. This review firstly gives an overview of the pathophysiology of glaucoma as well as current treatment options including conventional and novel delivery strategies. It then summarizes the rational for neuroprotection as a novel therapy for glaucomatous neuropathies and reviews current potential neuroprotective strategies to preserve RGC, with a focus on connexin43 (Cx43) gap junction channel blockers.

Fundamentals and Advances in Tonometry.

According to the World Health Organization, glaucoma is the leading cause of irreversible blindness worldwide. Although intraocular pressure (IOP) is not considered any more to be a defining feature of the disease, its lowering remains the only treatment option for glaucoma. Therefore, accurate and precise measurement of IOP is the cornerstone of glaucoma. Intraocular pressure is a highly dynamic physiological parameter with individual circadian rhythms. The main limitation of current tonometry methods remains the static and mostly office-based nature of their measurements. This review provides a brief historical overview on tonometry and discusses current tonometry instruments. In recent years, approaches to 24-hour IOP monitoring have been introduced, and there is hope that they may become part of routine clinical management in the future.

An emerging treatment option for glaucoma: Rho kinase inhibitors.

Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics with multiple compounds currently in Phase II and III US Food and Drug Administration trials in the United States. These selective agents work by relaxing the trabecular meshwork through inhibition of the actin cytoskeleton contractile tone of smooth muscle. This results in increased aqueous outflow directly through the trabecular meshwork, achieving lower intraocular pressures in a range similar to prostaglandins. There are also animal studies indicating that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion cell survival, and reduce bleb scarring in glaucoma surgery. Given the multiple beneficial effects for glaucoma patients, ROCK inhibitors are certainly a highly anticipated emerging treatment option for glaucoma.

Provider use of collaborative goal setting with glaucoma patients.

The purpose of this preliminary study was to describe the extent to which providers used collaborative goal setting and individualized assessment with patients who were newly prescribed glaucoma medications. English-speaking glaucoma suspect patients from six ophthalmology clinics who were newly prescribed glaucoma medications had their medical visits videotaped and were interviewed after the visits. The videotapes were transcribed and coded to examine provider use of collaborative goal setting and individualized assessment. Fifty-one patients seeing 12 ophthalmologists participated. Providers gave patients glaucoma treatment options during 37% of the visits; only five providers gave patients treatment options Providers asked for patient treatment preferences in less than 20% of the visits; only two providers asked for patient treatment preferences. Providers were significantly more likely to ask African American patients for their preferences or ideas concerning treatment than non-African American patients (Pearson χ² = 4.1, p = 0.04). Providers were also significantly more likely to ask African American patients about their confidence in using glaucoma medication regularly than non-African American patients (Pearson χ² = 8.2, p = 0.004). Providers asked about patient views about glaucoma in less than 20% of the visits; five providers asked patients their views on glaucoma and its treatment. Providers were significantly more likely to ask African American patients about their views on glaucoma than non-African American patients (Pearson χ² = 5.62, p = 0.02). Eye care providers often did not use collaborative goal setting or conduct individualized assessments of patient views on glaucoma when prescribing treatment for the first time.

Selective laser trabeculoplasty (SLT) vs other treatment modalities for glaucoma: systematic review

Systemic review to compare selective laser trabeculoplasty (SLT) to other glaucoma treatment options in terms of their intraocular pressure (IOP)-lowering effect. Searches of the following databases were performed: PubMed, Cochrane Central Register of Controlled Trials, Ovid, EMBASE, metaRegister of Controlled Trials, and ClinicalTrials.gov. Only randomised controlled trials (RCTs) published in peer-reviewed journals comparing SLT to other glaucoma treatment options were considered. The main outcome measure was the change in IOP from baseline. An initial search of PubMed identified 23 RCTs with 17 meeting the inclusion criteria. Nine RCTs compared 180° SLT to 180° argon laser trabeculoplasty (ALT) and one trial compared 360° SLT to 360° ALT, all reporting no difference in terms of IOP reduction from baseline. One RCT reported better outcomes with SLT at 1 year but this effect regressed at 2 years. Three trials compared 360° SLT to medical therapy and found no difference between the two treatment options. One trial found greater IOP reduction with latanoprost vs 90° and 180° SLT, and greater IOP reduction with 180° and 360° SLT versus 90° SLT, however no differences were found between 360° SLT versus latanoprost or 360° vs 180° SLT. Two trials compared 180° SLT to 360° SLT finding no difference in IOP reduction. Two trials compared 180° SLT to 90° SLT, one finding no significant difference and one finding greater IOP reduction with 180° SLT over 90° SLT. One trial compared excimer laser trabeculotomy (ELT) to 180° SLT, finding no differences in IOP reduction up to 3 months follow-up but greater IOP reduction with ELT at time intervals between 9 and 24 months. There were no RCTs identified that compared SLT to surgery. In terms of the IOP lowering effect, there is no difference between SLT and ALT. Three trials indicate no difference between 360° SLT and medical therapy, with one of the trials indicating greater IOP reduction with latanoprost over 90° and 180° SLT. Three trials indicate no difference between 180° SLT and 360° SLT. It is inconclusive whether 90° is less efficacious than 180° SLT. One trial reports greater IOP reduction with ELT over 180° SLT in the long term.

Diode laser endoscopic cyclophotocoagulation in the normal equine eye

To determine the clinical and histologic effects of diode endoscopic cyclophotocoagulation (ECP) in the phakic equine eye. Phase I: 10 equine cadaver eyes. Phase II: four normal adult horses. Phase I: ECP probe angle of reach (AR) was determined. Multiple ECP energy levels: 0.75, 0.90, 1.05, 1.20, 1.35, 1.50 J, and the resulting visible and histologic ciliary process changes were evaluated. Phase II: Ocular quadrants were treated with ECP at 0.90, 1.14, 1.38 J, and a control. The contralateral eye underwent a sham operation. Tissue changes (clinical and histologic) were evaluated. Phase I: Mean combined AR was 162 ± 29 degrees. Mean visible tissue scores: 2.60 ± 0.58 (0.75 J) to 5.04 ± 0.30 (1.50 J) from possible total of 6. Tissue 'popping' was observed at 1.50 J. Histologic ciliary tissue damage was present at all settings. Phase II: Mean visible tissue scores: 2.90 ± 0.48 (0.90 J), 3.61 ± 0.57 (1.14 J), and 4.52 ± 0.56 (1.38 J). Tissue 'popping' was observed at 1.38 J. Histologic ciliary tissue damage was present at all settings. Clinical effects included acute inflammation, intraocular pressure reduction, cataract formation, corneal edema, corneal ulceration, and postoperative ocular hypertension. Diode ECP between 0.90 and 1.14 J is a potential treatment option for glaucoma in horses based on visible tissue effects and target ciliary epithelium damage. Iatrogenic cataract development may limit the use of an anterior chamber approach in phakic horses. Supported in part by an ACVO VAF grant.

A randomized, 36-month, post-marketing efficacy and tolerability study in Sweden and Finland of latanoprost versus non-prostaglandin therapy in patients with glaucoma or ocular hypertension

To compare the effect of time on therapy, efficacy, tolerability and resource utilization of latanoprost or non-prostaglandin analogues (non-PGs) in patients who required a change in intraocular pressure (IOP)-lowering monotherapy. This open-label, multicentre study (Sweden, 19 sites; Finland, seven sites) included adults with glaucoma or ocular hypertension with mean diurnal IOP > or = 21 mmHg on ocular hypotensive monotherapy. Patients were randomized to latanoprost monotherapy or non-PG therapy (commercially available therapy other than a PG) and followed for 36 months. End-points included: time to treatment failure (baseline to visit with a change in/addition to treatment); diurnal IOP (mean of 08.00, 12.00 and 16:00 hr measurements) at months 6, 12, 24 and 36; tolerability; and resource utilization, where analyses used Swedish and Finnish 2006 unit costs. Three hundred and twenty-six patients received >or = 1 dose of latanoprost (n = 162) or non-PGs (n = 164). Median time to treatment failure was longer for latanoprost (36 months) than for non-PGs (12 months; p < 0.001); 51% and 24% of patients remained on randomized therapy after 36 months, respectively (p < 0.001). Decreases in mean diurnal IOP from baseline were significantly greater for latanoprost than for non-PGs at months 6 and 12 (p < 0.01). No serious adverse events were judged to be treatment-related. Mean total 36-month direct costs were similar in patients initiated with latanoprost and non-PGs. Patients who failed previous monotherapy remained on therapy longer when switched to latanoprost. Latanoprost's IOP-reducing effect and tolerability were sustained over the long term. Resource utilization and costs were generally similar in those initiating latanoprost or non-PG therapy.

Glaucoma Management in Patients With Osteo-odonto-keratoprosthesis (OOKP)

To report diagnostic modalities and treatment options for glaucoma in eyes with osteo-odonto keratoprosthesis (OOKP). Eyes that underwent OOKP were evaluated for glaucoma at the time of the first postoperative visit, then at 1 and 3 months after the procedure, and thereafter every 6 months. All eyes underwent stereo-biomicroscopic optic nerve head (ONH) assessment, kinetic (Goldmann perimetry) and automated static visual field testing, ONH photography, Heidelberg retina tomograph, scanning laser polarimetery (GDx), and optical coherence tomography. Treatment of glaucoma was also reviewed. Average follow-up period was 19.1 (range: 5 to 31) months. Of the 15 eyes that underwent OOKP, 5 eyes had preexisting glaucoma. None of the other 10 eyes developed glaucoma after OOKP. ONH photography and visual field testing were the most reliable methods to assess status of the disease, whereas Heidelberg retina tomograph and optical coherence tomography could be performed with reasonable reproducibility and quality; GDx imaging was poor. All patients with glaucoma were treated with oral acetazolamide 500 mg twice a day. Transscleral cyclophotocoagulation was performed in 3 eyes at stage 2 of OOKP surgery. Progression of glaucoma was noted in 2 eyes on the basis of optic disc photographs and automated perimetry. Visual field testing and optic disc assessment with optic disc photographs seem to be effective methods to monitor eyes with OOKP for glaucoma. Treatment strategies include oral medications to lower intraocular pressure and cyclophotocoagulation.

Management of Glaucoma: Focus on Pharmacological Therapy

Glaucoma represents a major cause of vision loss throughout the world. Primary open-angle glaucoma, the most common form of glaucoma, is a chronic, progressive disease often, though not always, accompanied by elevated intraocular pressure (IOP). In this disorder, retinal ganglion cell loss and excavation of the optic nerve head produce characteristic peripheral visual field deficits. Patients with normal-tension glaucoma present with typical visual field and optic nerve head changes, without a documented history of elevated IOP. A variety of secondary causes, such as pigment dispersion syndrome and ocular trauma, can result in glaucoma as well. Treatment of all forms of glaucoma consists of reducing IOP. With proper treatment, progression of this disease can often be delayed or prevented. Treatment options for glaucoma include medications, laser therapy and incisional surgery. Laser techniques for the reduction of IOP include argon laser trabeculoplasty and selective laser trabeculoplasty. Both techniques work by increasing outflow of aqueous humour through the trabecular meshwork. Surgical options for glaucoma treatment include trabeculectomy, glaucoma drainage tube implantation and ciliary body cyclodestruction. While each of these types of procedures is effective at lowering IOP, therapy usually begins with medications. Medications lower IOP either by reducing the production or by increasing the rate of outflow of aqueous humour within the eye. Currently, there are five major classes of drugs used for the treatment of glaucoma: (i) cholinergics (acetylcholine receptor agonists); (ii) adrenoceptor agonists; (iii) carbonic anhydrase inhibitors (CAIs); (iv) beta-adrenoceptor antagonists; and (v) prostaglandin analogues (PGAs). Treatment typically begins with the selection of an agent for IOP reduction. Although beta-adrenoceptor antagonists are still commonly used by many clinicians, the PGAs are playing an increasingly important role in the first-line therapy of glaucoma. Adjunctive agents, such as alpha-adrenoceptor agonists and CAIs are often effective at providing additional reduction in IOP for patients not controlled on monotherapy. As with any chronic disease, effective treatment depends on minimising the adverse effects of therapy and maximising patient compliance. The introduction of a variety of well tolerated and potent medications over the past few years now allows the clinician to choose a treatment regimen on an individual patient basis and thereby treat this disorder more effectively.

Standardisierte Akupunkturtherapie bei Patienten mit okulärer Hypertension oder Glaukom – Ergebnisse einer prospektiven Beobachtungsstudie

Standardized Acupuncture Therapy in Patients with Ocular Hypertension or Glaucoma – Results of a Prospective Observational Study Background: Glaucoma is one of the most frequent causes of blindness worldwide. The main risk factor for this optic nerve disease is high individual intraocular pressure. Objective: The aim of this observational study was to investigate the effect of acupuncture therapy on individual internal eye pressure in glaucoma and ocular hypertension patients. Material and Methods: 18 patients (11 female; age 38–75 years) with a diagnosis of glaucoma (n = 3) or ocular hypertension (n = 15) were included in this study. Patients received one session of a standardized acupuncture treatment (acupuncture points Liv 3, Li 4, Gb 37). Target parameters were the change in intraocular pressure and the compatibility of treatment. Measurements of intraocular pressure were carried out 15 min before, 15 min after, and 24 h after acupuncture. Results: Compared with the mean intraocular pressure in both eyes before treatment (21.94 ± 2.4 mm Hg), patients showed a significant decrease 15 min after treatment (–2.67 ± 1.34 mm Hg) as well as 24 h after treatment (–2.5 ± 2.13 mm Hg). There was no significant difference between the mean intraocular pressure at 15 min after treatment and at 24 h after treatment. No adverse events were observed. Conclusion: The results of this study indicate that acupuncture therapy may be a valid treatment option for glaucoma and ocular hypertension patients. Additional and, if possible, randomized studies investigating the effectiveness of acupuncture in the treatment of the above-mentioned conditions still need to be conducted.

Topical dorzolamide 2%/timolol 0.5%: a review of its use in the treatment of open-angle glaucoma.

The nonselective beta-blocker timolol and the carbonic anhydrase inhibitor dorzolamide both lower intraocular pressure (IOP). Timolol and dorzolamide have different mechanisms of action and their effects are additive when administered together. Therefore, the 2 drugs are frequently used concomitantly to treat patients with open-angle glaucoma who have not adequately responded to first-line therapy. A barrier to good compliance with concomitant therapy is the need to administer 5 or 6 drops of medication on 2 or 4 occasions during the day. Timolol 0.5% and dorzolamide 2.0% have therefore been combined in a single formulation, reducing the number of administrations required to 2 per day. Clinical trials in patients with glaucoma have demonstrated that dorzolamide 2%/timolol 0.5% (dorzolamide/timolol) is superior to monotherapy with the individual components. When dorzolamide/timolol administered twice daily was compared with concomitant treatment with dorzolamide 2% and timolol 0.5%, each administered twice daily for 90 days, both regimens resulted in marked lowering of trough IOP (measured just before the morning dose) compared with baseline (reduction in IOP = 4.2mm Hg). The effect of the 2 regimens on IOP at all time points, both before treatment and at peak effect (2 hours after treatment), were virtually indistinguishable. When the combined formulation was compared with a concomitant regimen that included dorzolamide 2% 3 times daily and timolol 0.5% twice daily the concomitant regimen was slightly more efficacious than the combined regimen at trough after 90 days: IOP was lowered by 3.6mm Hg in the combined group versus 4.1 mm Hg in the concomitant group. Dorzolamide/timolol has been compared with concomitant administration of timolol 0.5% and the IOP lowering miotic drug, pilocarpine 2.0%. This non-blind patient-preference study found that both regimens reduced IOP. However, the dorzolamide/timolol combination was preferred by the patients because of reduced frequency and severity of adverse effects and less frequent administration. Dorzolamide/timolol was well tolerated in clinical trials, the adverse effects reflected those of the individual components, and no additional tolerability issues were identified. However, the potential for timolol to cause cardiorespiratory effects must be considered when prescribing this combination. Furthermore, dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class of drug. Dorzolamide/timolol is a well tolerated and effective fixed combination for lowering IOP in the treatment of open-angle glaucoma and is likely to be useful in those patients who do not respond adequately to first-line monotherapy. Compared with concomitant therapy with the same 2 drugs the primary advantage is convenience, which may lead to improved compliance. Studies of compliance and comparisons with other currently available combination therapies would be useful to fully define the value of the formulation. Nonetheless, dorzolamide combined with timolol in a single applicator system will be a useful addition to the treatment options for glaucoma, a leading cause of preventable blindness.