Linnet Rodriguez, MD
Wills Eye Hospital, Philadelphia, PA
The Charles L Schepens lecture started with the introduction of the 16th recipient, Dr. Emily Y. Chew. The topic was Macular Telangiectasia Type 2 (MacTel 2), Tale of a Global Private and Public Collaboration. The macular telangiectasia project started in December 2003 with global collaborations among the United Kingdom, United States, Germany, France, Switzerland, Israel, and Australia. The major goal of the project was to develop an understanding of the natural history, pathogenesis, and risk factors of MacTel as well as to develop a classification system.
MacTel is a retinal neurodegenerative disease with primary involvement of Müller cells. Fundus findings are pertinent for retinal opacification, hyperpigmentation and choroidal neovascularization. Fluorescein angiography may show mild leakage in the late phase with hypofluorescence in areas of hyperpigmentation. OCT may show loss of the ellipsoid zone (EZ) as well as cavitary changes.
Under pathological conditions, Müller glial cells can protect photoreceptors from cell death through the production of neutrophil factors like ciliary neurotrophic factor (CNTF). In preclinical models of retinal degeneration, photoreceptor loss was rescued with intravitreal injection of CNTF. In fact, neutrophil factors given to mouse models that were “MacTel-like” showed functional and anatomical photoreceptor cell rescue. This data supported the investigation of CNTF as a potential therapy for MacTel.
In order to produce CNTF, an encapsulated cell therapy model was developed. Revakinagene taroretcel (NT-501) houses NTC-201-6A cells. They are allogenic retinal pigmented epithelial cells with a unique CNTF expression vector that produces sustained levels of CNTF. It is surgically implanted in the vitreous cavity and anchored to the sclera.
Clinical trials of CNTF in patients with MacTel were therefore designed. Phase 1 was successfully completed in 2014 to evaluate the safety of this cell therapy. Phase 2 was designed as a randomized, sham-controlled trial. It was completed in 2017. It showed that ellipsoid zone (EZ) area loss from baseline was significantly less in those receiving NT-501 compared to sham through 36 months. There was also preservation of retinal sensitivity and reading speed in individuals receiving NT-501. Phase 3 consisted of a randomized sham-controlled study to evaluate the efficacy and safety of NT-501. It was performed at 47 international sites. It showed that treatment with NT-501 led to reduction in photoreceptor loss through 2 years compared to sham. Reading speed was also better preserved in those receiving NT-501. NT-501 was well tolerated with most ocular treatment emergent adverse events (TEAE) being mild and transient. Few of the serious TEAE reports were related to surgery. There was no endophthalmitis or ischemic optic neuropathy. These results demonstrated that intraocular delivery of CNTF using NT-501 encapsulated cell therapy was safe and effective for the treatment of Mac tel.
There was also an emphasis on developing a classification system for MacTel to facilitate better communication among clinicians and researchers.