Retinitis pigmentosa - Emerging treatments

General considerations

Current strategies for novel therapies include neuroprotection, small-molecule drugs, stem-cell based therapy, and retinal prosthesis. As with all emerging therapies, care must be taken to account for biased investigator observations and placebo effect in the design of clinical trials, as well as the critical analysis of data and responsible promotion of any potential treatment.[67]

Neuroprotection

The goal of neuroprotection is to deliver factors that prevent retinal neurons from degenerating. One potentially successful compound in animal studies has been ciliary neurotrophic factor (CNTF). A study in patients with geographic atrophy due to age-related macular degeneration showed that a subgroup of patients with CNTF implants retained better visual acuity than those who received sham treatment.[68] One large multicenter sham-surgery-controlled dose-ranging clinical trial investigated the long-term delivery of CNTF to the retina, using an encapsulated cell technology, for the treatment of retinitis pigmentosa (RP).[69][70] Patients were randomly assigned to receive a high- or low-dose implant in one eye and sham surgery in the other eye. The results demonstrated a dose-dependent increase in retinal thickness without any serious adverse events related to either the encapsulated cell implant or the surgical procedure; however, there was no therapeutic effect on visual acuity or visual-field sensitivity after 12 months in late-stage and early-stage disease, respectively. A trial using the calcium-channel blocker nilvadipine demonstrated preservation of central visual fields in a small group of patients with RP.[71] Similarly, topical unoprostone isopropyl was shown to preserve macular sensitivity after one year of treatment in a small group of patients with RP.[72] Larger, multicenter double-blinded clinical trials are needed to confirm the efficacy of these neuroprotective agents. Further clinical trials of neuroprotection are currently underway exploring other neuroprotective approaches for RP, including the use of methotrexate to promote the clearance of misfolded rhodopsin proteins, and the use of oral acetylcysteine to reduce oxidative stress in the retina.[73][74][75][76]

Cell- and stem cell-based therapy

Transplantation of various precursor cells into the subretinal space have been attempted to regenerate retinal pigment epithelial cells.[77] One study demonstrated the safety of injecting autologous bone-marrow-derived mononuclear cells in 5 patients with retinal degeneration; further studies are needed to evaluate the efficacy and safety of cell-based therapies.[78] With the advent of induced pluripotent stem cells that can be generated from the adult cells of patients with RP, not only can future cell-based replacement strategies be tailored to each individual but also new in-vitro techniques can be developed to better understand specific disease mechanisms and test the efficacy of therapies prior to clinical trials.[79]

Electronic retinal implants

Several groups have developed silicon microelectrodes for patients with profound vision loss from diseases such as RP. Such devices convert visual stimuli into electronic signals, which can stimulate photoreceptor cells in the retina.[80][81][82] These implants are best suited to the treatment of advanced disease where patients have residual visual acuity of light perception in their better eye. Although there is severe attenuation of the outer retina and disorganization of the inner retina in late-stage RP, the residual retinal nerve fiber layer is relatively preserved and susceptible to electrical stimulation, which can produce artificial vision in the form of perceived phosphenes. The Food and Drug Administration (FDA) approved the Argus II device for use within the US in February 2013. One single-center study evaluating 12-month safety and efficacy outcomes in 6 patients with RP showed the Argus II device to be well-tolerated.[83] With rigorous rehabilitation, the patients generally experienced limited improvement in visual function. However, this device was discontinued in 2019 and is no longer available. Other types of retinal prostheses are under development and testing in clinical trials, such as the second-generation (44-channel) suprachoroidal retinal prosthesis.[84][85]