Think Global – Act Local: Intravitreal Drug Delivery Systems in Chronic Noninfectious Uveitis

Abstract

The eye is probably the most attractive site of the body for treatment using locally delivered therapeutic agents. An ideal indication for such an approach is noninfectious posterior uveitis. Since intraocular structures of the posterior segment are difficult to reach and are otherwise accessible only by systemic treatment, current interest is focused on the pros and cons of intravitreal drug delivery. Because of its chronic and recurrent nature, the long-term release of anti-inflammatory agents is a major treatment goal. Intravitreal injections, intravitreal implants and biodegradable devices are the most commonly used and approved approaches to deliver various agents to the vitreous. Because of their broad and potent effects, corticosteroids (CS) have been the first-line candidates for intraocular delivery. An increasing spectrum of CS preparations including nondegradable and biodegradable devices is currently available. Since repeated and long-term applications bear the risk of steroid-related complications such as increased intraocular pressure and cataract, alternative agents are currently being tested. Intravitreal injection of methotrexate, anti-VEGF (vascular endothelial growth factor), anti-TNFα (tumor necrosis factor α) and sirolimus have also been applied in patients with conflicting results. Intravitreal treatment has significantly reduced the incidence of adverse effects compared to systemic application, but due to greater ocular side effects there are still some limitations.

Multimonth controlled small molecule release from biodegradable thin films

“…For example, antibacterial therapy typically requires sustained local concentrations for periods of days to weeks, whereas some diseases, such as tuberculosis, necessitate daily doses of antibiotics for at least 6 mo (1). Other diseases also have demonstrated benefits from a long-term multimonth drug regimen, including cystic fibrosis (2), ankylosing spondylitis (3), and chronic uveitis (4).…”

Posterior Segment Drug Delivery Devices: Current and Novel Therapies in Development

“…It releases active drug at a rate of 0.3-0.4 mcg/day over a period of *2.5 years. [14][15][16] Several studies have demonstrated its efficacy in reducing recurrence, improving vision, better control of inflammation compared to systemic therapy, and reducing the need for systemic immunosuppressive medication in noninfectious posterior uveitis and panuveitis. [16][17][18][19] A randomized, controlled, phase II/III trial demonstrated a lower rate of recurrence of uveitis in Retisertimplanted eyes (18.2%) compared with those receiving systemic corticosteroids (63.5%).…”

Introduction of the Mini Review Series in <b><i>Ophthalmic Research</i></b>

“…The first of these Mini Reviews will be found in this volume of Ophthalmic Research [1]. We start with a topic that has been a focus of the journal for several years: intravitreal drug delivery.…”