Sustained release glaucoma therapies: Novel modalities for overcoming key treatment barriers associated with topical medications

Abstract

Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness. The disease has conventionally been characterized by an elevated intraocular pressure (IOP); however, recent research has built the consensus that glaucoma is not only dependent on IOP but rather represents a multifactorial optic neuropathy. Although many risk factors have been identified ranging from demographics to co-morbidities to ocular structural predispositions, IOP is currently the only modifiable risk factor, most often treated by topical IOP-lowering medications. However, topical hypotensive regimens are prone to non-adherence and are largely inefficient, leading to disease progression in spite of treatment. As a result, several companies are developing sustained release (SR) drug delivery systems as alternatives to topical delivery to potentially overcome these barriers. Currently, Bimatoprost SR (Durysta TM ) from Allergan plc is the only FDA-approved SR therapy for POAG. Other SR therapies under investigation include: bimatoprost ocular ring (Allergan) (ClinicalTrials.gov identifier: NCT01915940), iDose ® (Glaukos Corporation) (NCT03519386), ENV515 (Envisia Therapeutics) (NCT02371746), OTX-TP (Ocular Therapeutix) (NCT02914509), OTX-TIC (Ocular Therapeutix) (NCT04060144), and latanoprost free acid SR (PolyActiva) (NCT04060758). Additionally, a wide variety of technologies for SR therapeutics are under investigation including ocular surface drug delivery systems such as contact lenses and nanotechnology. While challenges remain for SR drug delivery technology in POAG management, this technology may shift treatment paradigms and dramatically improve outcomes.

A Narrative Review of Ocular Surface Disease Related to Anti-Glaucomatous Medications

“…iDOSE can constantly release travoprost for 6-12 months. The phase II trial found that iDOSE exhibited an equal IOP reduction effect to timolol [136]. This system showed no adverse effects on conjunctiva and cornea.…”

Intraocular nano-microscale drug delivery systems for glaucoma treatment: design strategies and recent progress

“…1). Although many risk factors have been identified, such as ocular structural predisposition, increased intraocular pressure (IOP) is the only modifiable risk factor at present [11][12][13]. IOP is most often controlled by the daily dose of IOP-lowering eye drops [11,14].…”

“…Although many risk factors have been identified, such as ocular structural predisposition, increased intraocular pressure (IOP) is the only modifiable risk factor at present [11][12][13]. IOP is most often controlled by the daily dose of IOP-lowering eye drops [11,14]. Current anti-glaucoma management is conducted in a stepwise fashion and starts with single topical hypotensive eye drops [11].…”

“…IOP is most often controlled by the daily dose of IOP-lowering eye drops [11,14]. Current anti-glaucoma management is conducted in a stepwise fashion and starts with single topical hypotensive eye drops [11]. These eye drop medications typically lower the IOP through alteration of aqueous humour dynamics, either reducing its production (beta-blockers, alpha-agonists, carbonic anhydrase inhibitors) or increasing its outflow (pilocarpine, epinephrine, prostaglandin analogues (PGA)) [12,13].…”

Verbesserung der Tropfenanwendungsrate bei Glaukomen

“…Da die wesentlichen Gründe für eine nicht korrekte Behandlung in Vergesslichkeit, mangelnder Motivation, Schwierigkeiten bei der Applikation von Augentropfen und Zweifel am glaukomatösen Sehverlust und dessen Vorbeugung bestehen, ist verständlich, dass ein gezieltes Ansprechen bzw. ein Training hinsichtlich dieser Faktoren die Compliance signifikant verbessert [4, 5]. Allerdings war der zeitliche Aufwand mit einem jeweils 45-minütigen Gespräch nicht unerheblich.…”