Management of toxic optic neuropathy via a combination of Wharton's jelly-derived mesenchymal stem cells with electromagnetic stimulation

Purpose To investigate the effect of the combination of Wharton's jelly derived mesenchymal stem cells (WJ-MSC) and high frequency repetitive electromagnetic stimulation (rEMS) in the therapy of toxic optic neuropathies with severe symptoms after the available current therapy modalities which were unsucessful. Material and methods This prospective, open-label clinical phase-3 study was conducted at Ankara University Faculty of Medicine, Department of Ophthalmology between April 2019 and April 2021. Thirty-six eyes of 18 patients with toxic optic neuropathy (TON) were included in the study. Within 1-3 months after the emergency interventions, patients with various degrees of sequela visual disturbances were studied in this clinical trial. The cases were divided into three groups according to similar demographic characteristics. Group 1: Consists of 12 eyes of 12 patients treated with the WJ-MSC and rEMS combination in one eye. Group 2: Consists of 12 eyes of 12 patients treated with only rEMS in one eye. Group 3: Consists of 12 eyes of six patients treated with only WJ-MSC in both eyes. The course was evaluated by comparing the quantitive functional and structural assessment parameters measured before and at the fourth month of applications in each group. Results The mean best corrected visual acuity (BCVA) delta change percentages of the groups can be ranked as: Group 1 (47%) > Group 3 (32%) > Group 2 (21%). The mean fundus perimetry deviation index (FPDI) delta change percentages of the groups can be ranked as: Group 1 (95%) > Group 2 (33%) > Group 3 (27%). The mean ganglion cell complex (GCC) thickness delta change (decrease in thickness) percentages can be ranked as: Group 1 (- 21%) > Group 3 (- 15%) > Group 2 (- 13%). The visual evoked potential (VEP) P100 latency delta change percentages of the groups can be ranked as: Group 1 (- 18%) > Group 3 (- 10%) > Group 2 (- 8%). The P100 amplitude delta change percentages of the groups can be ranked as: Group 1 (105%) > Group 3 (83%) > Group 2 (24%). Conclusion Toxic optic neuropathies are emergent pathologies that can result in acute and permanent blindness. After poisoning with toxic substances, progressive apoptosis continues in optic nerve axons and ganglion cells. After the proper first systemic intervention in intensive care clinic, the WJ-MSC and rEMS combination seems very effective in the short-term period in cases with TON. To prevent permanent blindness, a combination of WJ-MSC and rEMS application as soon as possible may increase the chance of success in currently untreatable cases. Trial Registration ClinicalTrials.gov ID: NCT04877067.

Automated summary

The combination of WJ-MSC and high frequency rEMS therapy showed significant improvement in visual acuity and optic nerve structure in patients with toxic optic neuropathies. This combination therapy may offer a promising approach for currently untreatable cases, potentially preventing permanent blindness.