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

Abstract

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.

Keywords: Amiodarone; Carbon dioxide; Electromagnetic stimulation; Methanol; Sildenafil; Stem cell; Toxic optic neuropathy; Wharton’s jelly-derived mesenchymal stem cell.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1

a The phenotypic characterization of Wharton jelly derived mesenchymal stem cells before cryopreservation. b The phenotypic characterization of Wharton jelly derived mesenchymal stem cells after cryopreservation

Fig. 1

a The phenotypic characterization of Wharton jelly derived mesenchymal stem cells before cryopreservation. b The phenotypic characterization of Wharton jelly derived mesenchymal stem cells after cryopreservation

Fig. 2

Retinal electromagnetic stimulator (rEMS) device. Application of the helmet to stimulate the retina-optic nerve and visual pathways [–37]

Fig. 3

a Visual field enlargement according to study timepoints (T0, T2) in the eye treated with combination of WJ-MSC and rEMS. Note the change in FPDI values (Table 1, patient 1: left eye). (a) Before application, FPDI 49% (b) at 4th month, FPDI 69%. b Visual field enlargement according to study timepoints (T0, T2) in the eye treated with only rEMS. Note the change in FPDI values (Table 2, patient 1: right eye). (a) Before application, FPDI 61% (b) at 4th month, FPDI 71%

Fig. 4

a Visual field enlargement according to study timepoints (T0, T2) in the eye treated with combination of WJ-MSC and rEMS. Note the change in FPDI values (Table 1, patient 3: left eye). (a) Before application, FPDI 34% (b) at 4th month, FPDI 98%. b Visual field enlargement according to study timepoints (T0, T2) in the eye treated with only rEMS. Note the change in FPDI values (Table 2, patient 3: right eye). (a) Before application, FPDI 49% (b) at 4th month, FPDI 72%

Fig. 5

a Visual field enlargement according to study timepoints (T0, T2) in the eye treated with combination of WJ-MSC and rEMS. Note the change in FPDI values (Table 1, patient 4: left eye). (a) Before application, FPDI 47% (b) at 4th month, FPDI 65%. b Visual field enlargement according to study timepoints (T0, T2) in the eye treated with only rEMS. Note the change in FPDI values (Table 2, patient 4: right eye). (a) Before application, FPDI 46% (b) at 4th month, FPDI 53%

Fig. 6

a Visual field enlargement according to study timepoints (T0, T2) in the eye treated with only WJ-MSC. Note the change in FPDI values (Table 3, patient 1: right eye). (a) Before application, FPDI 61% (b) at 4th month, FPDI 78%. b Visual field enlargement according to study timepoints (T0, T2) in the eye treated with only WJ-MSC. Note the change in FPDI values (Table 3, patient 4: left eye). (a) Before application, FPDI 32% (b) at 4th month, FPDI 37%

Fig. 7

Improvement in “ganglion cell complex thickness” according to study timepoints (T0, T2) in the OD eye treated with combination of WJ-MSC and rEMS (Table 1, patient 2: right eye. (a) Before application, 92 µm, (b) at 4th month, 64 µm. Improvement in “ganglion cell complex thickness” according to study timepoints (T0, T2) in the OS eye treated with only rEMS (Table 2, patient 2: left eye. (a) Before application, 88 µm, (b) at 4th month, 78 µm

Fig. 8

Improvement in “ganglion cell complex thickness” according to study timepoints (T0, T2) in the OD eye treated with combination of WJ-MSC and rEMS (Table 1, patient 5: right eye. (a) Before application, 94 µm, (b) at 4th month, 60 µm. Improvement in “ganglion cell complex thickness” according to study timepoints (T0, T2) in the OS eye treated with only rEMS (Table 2, patient 5: left eye. (a) Before application, 89 µm, (b) at 4th month, 64 µm

Fig. 9

Improvement in “pattern VEP” according to study timepoints (T0, T2) in the eye treated with combination of WJ-MSC and rEMS (Table 1, patient 6: left eye). a Before application, P100 latency 139 ms, P100 amplitude 2.9 mV b at 4th month, P100 latency 106 ms, P100 amplitude 6.3 mV

Fig. 10

Improvement in “pattern VEP” according to study timepoints (T0, T2) in the eye treated with combination of WJ-MSC and rEMS (Table 1, patient 7: left eye). a Before application, P100 latency 140 ms, P100 amplitude 3.6 mV b at 4th month, P100 latency 118 ms, P100 amplitude 7.1 mV

Fig. 11

Improvement in “pattern VEP” according to study timepoints (T0, T2) in the eye treated with only WJ-MSC (Table 3, patient 6: left eye). a Before application, P100 latency 152 ms, P100 amplitude 1.6 mV b at 4th month, P100 latency 152 ms, P100 amplitude 6.5 mV