Fixed-combination intraocular pressure-lowering therapy for glaucoma and ocular hypertension: advantages in clinical practice

Holló, Gábor; Topouzis, Fotis; Fechtner, Robert D.

doi:10.1517/14656566.2014.936850

Cited by 96 publications

(87 citation statements)

References 95 publications

(36 reference statements)

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“…Use of fixed combinations may partly reduce this problem, because of less frequent instillation and lower exposure to toxic preservatives, thereby reducing the problem of ocular surface disease. 108,109 Until recently, all fixed combinations included beta-receptor antagonists with either parasympathomimetics, prostaglandin analogues or carbonic anhydrase inhibitors. Recently, however, a fixed combination between brimonidine and brinzolamide entered the market.…”

Section: Systemic Therapiesmentioning

confidence: 99%

Pharmacotherapy of Glaucoma

Schmidl

Schmetterer²,

Garhöfer³

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

129

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Glaucoma is a group of diseases involving the optic nerve and associated structures, which is characterized by progressive visual field loss and typical changes of the optic nerve head (ONH). The only known treatment of the disease is reduction of intraocular pressure (IOP), which has been shown to reduce glaucoma progression in a variety of large-scale clinical trials. Nowadays, a relatively wide array of topical antiglaucoma drugs is available, including prostaglandin analogues, carbonic anhydrase inhibitors, beta-receptor antagonists, adrenergic agonists, and parasympathomimetics. In clinical routine, this allows for individualized treatment taking risk factors, efficacy, and safety into account. A major challenge is related to adherence to therapy. Sustained release devices may help minimize this problem but are not yet available for clinical routine use. Another hope arises from non-IOP-related treatment concepts. In recent years, much knowledge has been gained regarding the molecular mechanisms that underlie the disease process in glaucoma. This also strengthens the hope that glaucoma therapy beyond IOP lowering will become available. Implementing this concept with clinical trials remains, however, a challenge.

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Section: Systemic Therapiesmentioning

confidence: 99%

Pharmacotherapy of Glaucoma

Schmidl

Schmetterer²,

Garhöfer³

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

129

View full text Add to dashboard Cite

show abstract

“…Furthermore, due to simplification of the instillation regimen, fixed combinations may improve treatment adherence and persistence. Therefore, fixed combinations enhance the stability of IOP control over time [16][17][18] . The toxic effects of preservatives are dose dependent and cumulative.…”

Section: Discussionmentioning

confidence: 99%

Open-Angle Glaucoma: Drug Development Pipeline during the Last 20 Years (1995-2015)

et al. 2017

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Objectives: To analyse drug development for open-angle glaucoma during the last 20 years. Methods: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition “open-angle glaucoma” with the intervention “drug” was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered. Results: We recorded 158 studies for the condition of open-angle glaucoma with a drug-based intervention; 65 of the studies reported phase 2 trials and 74 reported phase 3 trials. Pharmaceutical companies were the primary sponsors of 95.3% of the trials. Most of the studies (66.5%, n = 105) involved a new drug, and the remainder (33.5%, n = 53) tested fixed drug associations. The bulk of the trials (n = 99, 62.7%) involved the use of prostaglandin analogues, either as a comparator or a study drug. In descending order of frequency, the studies conducted involved Rho-kinase inhibitors (n = 15), carbonic anhydrase inhibitors (n = 14), β-blockers (n = 7), angiostatic steroids (n = 6), α₂-adrenergic agonists (n = 4), 5-HT_2A receptor agonists (n = 4), and NMDA receptor antagonists (n = 2). A cyclin-dependent kinase inhibitor, an LIM-domain kinase 2 inhibitor, an A1 adenosine receptor agonist, catechin, macrolide, saffron, and seawater were each tested in 1 clinical trial. Conclusion: Research into the medical treatment of glaucoma indicates the use of prostaglandin analogues. However, there are a significant number of trials testing other drug classes, particularly Rho-kinase inhibitors. This new focus could lead to a potential increase in the number of therapeutical options for the management of glaucoma in the future.

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“…[31][32][33][34][35][36][37][38] In recent years, patients whose IOP is uncontrolled by the single-agent ocular hypotensive drugs, or those who no longer respond to a given medication, need to be placed on adjunctive therapy such as PG agonist drops instilled at night being supplemented during the day with eyedrops of a beta-blocker or a CAI. 39,40 Some patients may need 3 or more different classes of drugs to bring down their IOP to an acceptable level (12-16 mmHg). 39,40 To accommodate such patients, various fixed-dose combination drugs in a single bottle have been approved to treat POAGassociated elevated IOP.…”

Section: Ocular Hypertensive Pharmacotherapy: Present Day Treatmentsmentioning

confidence: 99%

“…39,40 Some patients may need 3 or more different classes of drugs to bring down their IOP to an acceptable level (12-16 mmHg). 39,40 To accommodate such patients, various fixed-dose combination drugs in a single bottle have been approved to treat POAGassociated elevated IOP. Examples of the latter combination formulations include Cosopt (dorzolamide 2% + timolol 0.5%), Combigan (brimonidine 0.2% + timolol 0.5%), Azarga (brinzolamide 1% + timolol 0.5%), Duotrav (travoprost 0.004% + timolol 0.5%), and Simbrinza (brinzolamide 1% + brimonidine 0.2%).…”

Section: Ocular Hypertensive Pharmacotherapy: Present Day Treatmentsmentioning

confidence: 99%

“…Examples of the latter combination formulations include Cosopt (dorzolamide 2% + timolol 0.5%), Combigan (brimonidine 0.2% + timolol 0.5%), Azarga (brinzolamide 1% + timolol 0.5%), Duotrav (travoprost 0.004% + timolol 0.5%), and Simbrinza (brinzolamide 1% + brimonidine 0.2%). 39,40 Even a triple fixed-dose combination formulation has been prepared and shown to lower IOP to a significant extent and beyond the individual drug contributions (dorzolamide + brimonidine + timolol). 39 Even though the various drugs and combination products ( Table 1) mentioned above are proving helpful in clinically managing the elevated IOP, they all have ocular and/or systemic side effects that limit their utility constrained by their posology, overall effectiveness, duration of action, and/ or significant side effects.…”

Section: Ocular Hypertensive Pharmacotherapy: Present Day Treatmentsmentioning

confidence: 99%

See 1 more Smart Citation

Novel Potential Treatment Modalities for Ocular Hypertension: Focus on Angiotensin and Bradykinin System Axes

Sharif

2015

Journal of Ocular Pharmacology and Therapeutics

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Despite the availability of modern surgical procedures, new drug delivery techniques, health authority-approved single topical ocular drugs, and combination products thereof, there continues to be an unmet medical need for novel treatment modalities for preserving vision. This is especially true for the treatment of glaucoma and the high risk factor often associated with this ocular disease, elevated intraocular pressure (IOP). Undesirable local or systemic side effects, frequency of dosing, lack of sustained IOP lowering, and lack of prevention of diurnal IOP spikes are among the greatest challenges. The very recent discovery, characterization, and publication of 2 novel IOP-lowering agents that pertain to the renin-angiotensin and kallikrein-kinin axes potentially offer novel means to treat and control ocular hypertension (OHT). Here, some contextual introductory information is provided first, followed by more detailed discussion of the properties and actions of diminazene aceturate (DIZE; a novel angiotensin-converting enzyme-2 activator) and FR-190997 (a nonpeptide bradykinin receptor-2 agonist) in relation to their anti-OHT activities in rodent and cynomolgus monkey eyes, respectively. It is anticipated that these compounds will pave the way for future discovery, development, and marketing of novel drugs to treat glaucoma and thus help save sight for millions of people afflicted with this slow progressive optic neuropathy.

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Fixed-combination intraocular pressure-lowering therapy for glaucoma and ocular hypertension: advantages in clinical practice

Cited by 96 publications

References 95 publications

Pharmacotherapy of Glaucoma

Pharmacotherapy of Glaucoma

Open-Angle Glaucoma: Drug Development Pipeline during the Last 20 Years (1995-2015)

Novel Potential Treatment Modalities for Ocular Hypertension: Focus on Angiotensin and Bradykinin System Axes

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