Neuroprotection in ophthalmology. Targets in the most frequent diseases. A clinician's point of view

Abstract

AbstractObjectives: To briefly review the most frequent ocular diseases in which a neuroprotective treatment would be needed and to present the results of a translational research based on the neuroprotective capacities of allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) in an ocular disease that currently lacks treatment, the non‐arteritic acute anterior ischemic optic neuropathy. (NA‐AION) considered as an infarct of the optic nerve head.Methods: After extensive preclinical evaluation of safety in rabbits, a prospective, non‐randomized, phase II clinical trial (Eudra CT number 2016–003029‐40 and ClinicalTrials.gov NCT03173638) was approved. Five patients with acute unilateral NA‐AION diagnosed within the first 2 weeks after symptom onset were included. After informed consent, patients received an intravitreal injection of 0.05 ml containing 150 μl of isotonic medium composed of Ringer's lactate, 0.5% human albumin, and 5 mM glucose, with a cell concentration of 1.5 × 106 cells/ml. The injection was administered using a 25‐gauge needle via the pars plana after topical anaesthesia. Patients were followed on days 1, 7, 30, 90, 180 and 1 year after injection. Safety was defined as the absence of an inflammatory reaction. The best‐corrected visual acuity, visual evoked potentials (VEP) and retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thicknesses were measured.Results: No patients had signs of intraocular inflammation at any time. An epiretinal membrane (ERM) developed in one patient. One phakic patient had a retrolental aggregate that did not progress to cataract. Four patients had visual improvement and three had increased amplitudes on the VEP recordings after treatment. The RNFL and GCL thicknesses decreased significantly in parallel with the visible papillary atrophy that developed during the follow‐up period.Conclusions: Despite development of an ERM in one patient and a possible cellular deposit in the retrolental space, the functional results are encouraging. A larger multicentre study of treated patients that includes a control group is currently running. The paracrine capacities of allergenic MSCs should be more extensively investigated in the clinic, taking advantage of their non‐immunogenicity, their ease of obtaining and their apparent safety.Financial support: Funded by Strategic Action in Health of the Institute of Health Carlos III (PIC18/00018), the Department of Regional Health of the Castilla y Léon Government (GRS 1928/A/19), and the Department of Education of the Castilla y León Regional Government (Grant VA077P17).