Endophthalmitis

Endophthalmitis is a condition whereby pathogens infect the eye and cause damage to numerous ocular cell types, which in turn can lead to irrevocable blindness.  The loss of ocular cells occurs as a result of both virulent replication and the uncontrolled inflammatory response that is as a natural response to infection.  This influx of inflammatory cells can destroy many of the native, non-dividing cells of the eye and is a major causative factor of blindness in patients with endophthalmitis.  Most endophthalmitis cases occur following the introduction of an infectious agent into the eye following trauma of a penetrating object into the eye, metastatic migration of bacteria from a distant infection site into the eye, or more commonly as a post-operative complication of cataract extraction and intravitreal injection.  Recent advances in the treatment for Age-related Macular Degeneration (AMD) have caused the incidence of endophthalmitis to nearly double, since AMD treatments are delivered by a monthly intravitreal injection.

Effective management of endophthalmitis relies heavily on prompt diagnosis and treatment.  Pathogen replication and inflammatory cell infiltration can occur rapidly and damage vision permanently.  The current standard of care for endophthalmitis is an intravitreal injection of fourth-generation fluoroquine antibiotics, such as Zymar (TM).  If endophthalmitis is diagnosed quickly, these antibiotics will destroy many virulent pathogens before a robust host-inflammatory response is activated.  Unfortunately, many cases of endophthalmitis are not caught in the initial stage of infection, so the antibiotics have little effect on preventing inflammatory influx into the eye.  For this reason, many ophthalmologists will deliver an intravitreal injection of a steroid, such as dexamethasone, concomitant with antibiotics.  This steroidal use is very controversial, and numerous clinical and animal studies have demonstrated that there is detrimental effect on ocular cells.  Although many ophthalmologists realize they are potential drawbacks to steroid use, they see it as a necessary risk; otherwise the uncontrolled inflammation will most likely result in vision loss.  Thus, the need exists to develop new anti-inflammatory treatments for endophthalmitis that can inhibit the propagation of inflammatory signaling and inflammatory cell infiltration without harming ocular cells.

Charlesson is developing novel anti-inflammatory therapies (CLT-004, CLT-005) to be used as adjuvant treatments with antibiotics in the clinical management of endophthalmitis. We believe the co-administration of these anti-inflammatory agents will prevent the severe ocular inflammation that leads to vision loss in endophthalmitis cases.