Surgical vs. medical retina. The separation used to be clear. Surgery dealt with anatomic pathologies including retinal detachments and epiretinal membranes. Medical approaches were applied for age-related macular degeneration, diabetic macular edema, etc.
Fortunately for the field and, most importantly, for our patients, promising development programs are blurring the line between our two historical silos.
Late last year, two global, randomized, sham-controlled Phase III trials enrolling 224 patients with macular telangiectasia type 2 found the NT-501 implant (Neurotech Pharmaceuticals) significantly reduced photoreceptor loss at month 24 by up to 66 percent. NT-501 uses encapsulated cell technology (ECT) to house human retinal pigment epithelial cells genetically modified to produce ciliary neurotropic factor (CNTF), a diffusible neuroprotective cytokine normally produced by Muller glial cells.
The device is surgically implanted into the vitreous through a 3-mm incision, anchored to the sclera. It has been shown to produce medication for more than 10 years. Its tiny pores allow nutrients and oxygen in and CNTF out, but prevent cellular migration out and block immune cell migration in. Emily Chew, MD, will be presenting the Phase III data at the American Society of Retina Specialists’ 41st annual scientific meeting in July. Regulatory engagement is also underway.
Another device, the Port Delivery System (Susvimo, Genentech/Roche), a surgically implanted reservoir that releases ranibizumab into the vitreous cavity over many months, has demonstrated impressive efficacy and durability in trials for neovascular AMD, DME and diabetic retinopathy. While it has been voluntarily recalled from the market, there is hope that the system may return commercially with some modifications.
On the flip-side, medical adjuncts are being investigated that may be able to improve outcomes for traditionally surgical diseases. For example, in the Phase III GUARD trial, a series of 12 intravitreal injections of the antimetabolite methotrexate demonstrated encouraging results in the management of retinal detachments complicated by proliferative vitreoretinopathy.
And ONL1204 (ONL Therapeutics), a peptide inhibitor of fas apoptosis signaling, is the subject of an ongoing sham-controlled Phase II trial of patients with macula-off rhegmatogenous RD. Fas inhibition can prevent cell death and may minimize damaging inflammatory cascades within the neurosensory retina driven by oxygen and nutrient deprivation during detachment and reperfusion injury upon reattachment.
In this spirit, our current edition is dedicated to surgical innovation as well as the surgeons and companies leading these important developments. As addressed directly by the decorated Navy SEAL and leadership author Jocko Willink, we will continue to “break down silos,” between medical and surgical retina, one pathology at a time. RS