Dataset Information

Intravitreal allogeneic mesenchymal stem cells: a non-randomized phase II clinical trial for acute non-arteritic optic neuropathy.

ABSTRACT:

Background

An effective treatment for acute non-arteritic ischemic optic neuropathy (NA-AION) has not been known or proven yet. Previous studies have suggested a neuroprotective effect of allogeneic bone marrow-derived mesenchymal stem cells. This study aims to report the results of a clinical trial on patients with acute non-arteritic optic neuropathy (NA-AION) treated with an intravitreal injection of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) (MSV®).

Methods

We conducted a prospective, non-randomized, clinical phase-II study (Eudra CT number 2016-003029-40; ClinicalTrials.gov Registry NCT03173638) that included 5 patients with acute unilateral NA-AION diagnosed within 2 weeks after symptom onset and who received an intravitreal injection of allogeneic BM-MSCs (0.05 ml; cell concentration: 1.5 × 10⁶cells/mL). The patients underwent regular ophthalmological examinations and were followed for one year.

Results

In this trial, allogeneic BM-MSCs appeared to be safe as no patients developed signs of acute nor chronic intraocular inflammation or a significant change in intraocular pressure, although an epiretinal membrane was developed in one patient. A retrolental aggregate formed shortly after the injection spontaneously disappeared within a few weeks in another phakic patient, leaving a subcapsular cataract. Visual improvement was noted in 4 patients, and amplitudes of P100 on the visually evoked potentials recordings increased in three patients. The retinal nerve fiber layer and macular ganglion cell layer thicknesses significantly decreased during the follow-up.

Conclusions

Besides the development of an epiretinal membrane in one patient, the intravitreal application of allogeneic BM-MSCs appeared to be intraocularly well tolerated. Consequently, not only NA-AION but also BM-MSCs deserve more clinical investigational resources and a larger randomized multicenter trial that would provide stronger evidence both about safety and the potential therapeutic efficacy of intravitreally injected allogeneic BM-MSCs in acute NA-AION.

Trial registration

Safety Assessment of Intravitreal Mesenchymal Stem Cells for Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NEUROSTEM). NCT03173638. Registered June 02, 2017 https://clinicaltrials.gov/ct2/show/NCT03173638 .

SUBMITTER: Pastor JC

PROVIDER: S-EPMC10512539 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Intravitreal allogeneic mesenchymal stem cells: a non-randomized phase II clinical trial for acute non-arteritic optic neuropathy.

Pastor Jose C JC Pastor-Idoate Salvador S López-Paniagua Marina M Para Marta M Blazquez Francisco F Murgui Esther E García Verónica V Coco-Martín Rosa M RM

Stem cell research & therapy 20230921 1

<h4>Background</h4>An effective treatment for acute non-arteritic ischemic optic neuropathy (NA-AION) has not been known or proven yet. Previous studies have suggested a neuroprotective effect of allogeneic bone marrow-derived mesenchymal stem cells. This study aims to report the results of a clinical trial on patients with acute non-arteritic optic neuropathy (NA-AION) treated with an intravitreal injection of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) (MSV®).<h4>Methods</h ...[more]

PMID: 37735668

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Project description:PurposeOptical coherence tomography reveals retinal ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thinning in chronic optic nerve injury. With acute optic nerve injury, as in acute nonarteritic anterior ischemic optic neuropathy (NAION), swelling obscures early demonstration of RNFL thinning, which might be used to evaluate therapies. We hypothesized that measurement of GCL plus inner plexiform layer (IPL) thickness and trajectory of thinning would show it is an earlier and more accurate biomarker of early permanent neuronal injury.MethodsWe prospectively studied 29 acute NAION eyes with standard automated perimetry and spectral domain (SD) optical coherence tomography for 6 months. We used a three-dimensional layer segmentation (method 1) and a commercial proprietary (method 2), to compute the combined thickness of macular GCL+IPL and method 2 to compute peripapillary RNFL thickness.ResultsAt presentation, the mean GCL+IPL thickness (78.7 μm ± 8.9) for NAION eyes, did not differ from unaffected fellow eyes (83 μm ± 6.4), using method 1 while method 2 (66.8 μm ± 18.7) failed in 34% of NAION eyes. At 1 to 2 months, 12% had RNFL loss compared to baseline, while 68% of NAION eyes had GCL+IPL thinning. The ganglion cell layer plus inner plexiform layer reduction was greatest at 1 to 2 months (19.6 μm ± 12.6) and was minimally worse after month 3. Ganglion cell layer plus inner plexiform layer thinning showed moderate to strong significant correlation with the visual acuity and mean deviation at each exam time. The retinal nerve fiber layer was not thinned until month 3.ConclusionsGanglion cell layer plus inner plexiform layer is acutely unaffected and provides a reliable measure of retinal neuronal structure using three-dimensional segmentation. Thinning develops within 1 to 2 months of onset, which is prior to RNFL swelling resolution. This suggests GCL+IPL measurement is better than the RNFL thickness to use as biomarker of early structural loss in NAION.

Project description:IntroductionThe peripapillary choroid shares a blood supply with and is directly apposed to the optic nerve, and therefore may contribute to the pathogenesis of non-arteritic anterior ischemic optic neuropathy (NAION). Prior studies evaluating peripapillary choroidal thickness (PCT) or choroidal vascularity index (CVI; the ratio of the perfused area to total choroid area) have produced mixed results. None investigated the relationship between PCT and CVI or demonstrated functional correlates. We hypothesized that greater PCT and lower CVI would correlate with visual function in patients presenting with NAION.MethodsSeventeen eyes with NAION (9 acute, 8 non-acute) and 6 unaffected "fellow" eyes in 13 patients, and 18 eyes in 18 age-matched control subjects were imaged using swept-source optical coherence tomography (SS-OCT) prospectively between 2017-2018. Mean PCT and CVI measurements were compared across groups and with respect to corresponding automated perimetric performance at the same visit.ResultsAnalysis of variance showed significantly greater PCT (NAION: 278 ± 65 μm, Fellow: 221 ± 50 μm, Control: 158 ± 27 μm, p<0.001) and lower CVI (NAION: 0.35 ± 0.03, Fellow: 0.35 ± 0.04, Control: 0.38 ± 0.02, p<0.005) in patients with NAION compared to control subjects. Bonferroni-corrected pairwise comparisons showed greater PCT and lower CVI in NAION-affected eyes compared to control eyes (p values<0.008), and no significant differences in PCT or CVI between NAION and fellow eyes (p values>0.06). PCT was negatively correlated with CVI among unaffected fellow eyes (r=-0.8, p<0.05), but not among acute NAION eyes (r=-0.1, p>0.7), non-acute NAION eyes (r=0.1, p>0.7), or controls (r=-0.3, p>0.2). Nasal CVI was positively correlated with mean deviation scores in non-acute NAION (r=0.8, p<0.02), but not among fellow unaffected eyes (r=0.8, p>0.05) or acutely affected NAION eyes (r=-0.3, p>0.4). Mean and temporal PCT correlated with pattern standard deviation scores among unaffected fellow eyes (r=0.8, p<0.04; r=0.9, p<0.03), but not among acute NAION eyes (r=-0.2, p>0.5; r=-0.1, p>0.7) or non-acute NAION eyes (r=0.1, p>0.7; r=0.05, p>0.9).ConclusionNAION and unaffected fellow eyes demonstrate increased choroidal thicknesses and reduced vascular density. Perimetric performance is directly associated with vascular density among non-acutely affected eyes with NAION. Ongoing work will provide further insights into these structure-function relationships with pathogenic and pathophysiologic relevance.

Dataset Information

Intravitreal allogeneic mesenchymal stem cells: a non-randomized phase II clinical trial for acute non-arteritic optic neuropathy.

Background

Methods

Results

Conclusions

Trial registration

Publications

Intravitreal allogeneic mesenchymal stem cells: a non-randomized phase II clinical trial for acute non-arteritic optic neuropathy.

Similar Datasets

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