Research published in the journal Translational Vision Science & Technology (TVST, 2014, Vol. 3, No. 6,Article 5) reports that a first-in-man study of a “posterior micro-pump drug delivery system” (or “PMP”), shows safety and tolerability following surgical implantion of the device for a period of 90 days. The novel ocular device, developed by Californian company, Replenish Inc., delivers a microdose of drug into the vitreous cavity and is designed to overcome limitations associated with the current necessity of repeat intravitreal injections for the treatment of disorders such as age-related macular degeneration (AMD) and diabetic macular edema (DME). The clinical study, led by Mark Humayuan and colleagues at the Keck School of Medicine University of Southern California, Los Angeles conducted the trial on 11 patients in Guadalajara, Mexico recording no serious or adverse events.
The single-centre, single arm open label prospective and non-randomized study was aimed at demonstrating safety and surgical feasibility of the micropump in patients with diabetic macular edema (DME). The rationale behind the development of the device arises from what the researchers describe as an increased “burden for physician, health system, and patients”, due to poor compliance with the regimen of multiple injections required over long periods of time. Such poor compliance, according to the researchers, can lead to irreversible vision loss while the necessity of repeated injections in itself increases the incidence of adverse events such as endophthalmitis and retinal detachment. As such, an alternative to repeat injections is likely to find significant favour with clincians treating AMD, DME and other ocular disorders. To meet the challenge, a miniaturised pump was constructed of titanium, silicone, and parylene using microelectromechanical system (MEMS) technology enabling the development of prototypes capable of delivering micro-doses in bench top tests and in demonstrating long-term safety when implanted in an animal models. According to the researchers, engineering tests on the devices show that the micropump can continue to function reliably for more than 100 programmable injections of intraocular drugs, including ranibizumab. The group estimate that “at a monthly dosing regimen, this could possibly represent more than 8 years of monthly intrvitreal injections”.
The surgical implantation of the micropump is understood to be similar to the implantation of a glaucoma drainage device and, with the first 11 trial patients, the procedure lasted on average 35 minutes. No serious adverse events were reported and no permanent decrease in the visual acuity were observed for any of the 11 implanted subjects. According to the formal publication, during the 4 to 6 weeks post-op period, all trial patients experienced a normal course of post-op healing of the conjunctiva, tenons, and cornea. In addition, “ocular motility was normal in primary gaze and all nine cardinal positions in the majority of the exams. Five patients reported transient diplopia on extreme vertical and horizontal duction in the first weeks postoperatively (abduction and elevation gaze), which completely resolved with the resolution of the periorbital edema”. Finally, when compared with the pre-implantation baseline assessments, all eyes in the study recorded either similar or improved visual acuity at day 90. Subsequent analysis will include assessment of drug viability at body tempersature given that the storage recommendations from such anti-VEGF medications may be recommened for below 4°C.