• Treatments for Preserving and Regenerating Retinal Ganglia


    Jeffrey L. Goldberg, MD, PhD, spoke at Saturday’s Glaucoma Subspecialty Day about promising new therapies that may protect and even regenerate retinal ganglion cells (RGCs).

    Rho and Rho-kinase (ROCK) inhibitors, such as netarsudil (Rhopressa, Aerie Pharmaceuticals) are next-generation IOP-lowering topicals that have demonstrated neuroprotective properties in preclinical studies. In rats with induced optic nerve trauma, “there was an increase in RGC survival when treated with topical ROCK inhibitors [compared with placebo]; and, similarly, we saw promotion of long-distance axon regeneration into the optic nerve,” said Dr. Goldberg. “Of course, we have to move this therapeutic testing into humans to confirm if these effects will bridge from animal testing.”

    Introducing stem cells into the vitreous may slow glaucomatous neurodegeneration, thanks to the myriad survival and growth factors that they produce. “The real long-term promise is whether we can turn stem cells into retinal ganglion cells and get them to wire up,” said Dr. Goldberg. “We are making enormous progress on both of these points.” Recent work showed success in turning human induced pluripotent stem cells into anatomically and electrophysically functional RGCs.

    Neurotrophic factors are a class of neuroenhancement drugs that augment or improve the function of RGCs, and they may provide more immediate results than neuroprotective therapies. One such therapy, ciliary neurotrophic factor (CNTF), has already shown an excellent safety profile in human trials. The treatment is delivered by implantation of a semipermeable membrane, right behind the lens, that is loaded with human cells that can secrete CNTF indefinitely. In a phase 1 trial for glaucoma, investigators saw improvement of visual field indices and retinal nerve fiber layer thickness within just 1 to 3 months. A randomized sham-controlled phase 2 trial has been planned.—Aliyah Kovner

    Financial disclosures. Dr. Goldberg: Aerie: C; Alcon Laboratories, Inc.: C; Allergan: C; Annexon: C; Inotek: C; Johnson & Johnson: C; NIH, DOD, GRF: S.

    Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.