Intravitreal Autologous Bone Marrow Derived Stem Cells in Ischemic Macular Edema - Results after 6 Months Follow-up

Abstract

Purpose: To investigate the effects and the safety of intravitreal autologous bone marrow-derived stem cells (auto-BMSC) in retinal vascular diseases with ischemic maculophaty.

Methods: Prospective, non-randomized clinical trial, including 15 patients (15 eyes) with ischemic macular edema due to diabetic retinopathy (DR), central retinal vein occlusion (CRVO) or central retinal artery occlusion (CRAO). Patients showed best-corrected visual acuity (BCVA) of 20/50, or worse, and no history of cancer or other ocular condition. In proliferative diabetic retinopathy (PDR), only patients without active neovascularization were included. Patients underwent intravitreal injection of approximately 10⁶ CD 34+ autologous bone marrow-derived cells (0.1 ml), and were evaluated before injection (baseline), and monthly during follow-up. A comprehensive ophthalmological evaluation was performed, including BCVA measurement, full field electroretinography (ERG - Diagnosys LLC), multifocal electroretinography (mfERG - Diagnosys LLC), and microperimetry (MAIA - Centervue) to access central (20 degrees) retinal sensitivity average threshold (AT), and the bivariate contour ellipse area (BCEA) as a measure of the fixation stability, to evaluate retinal function. Fluorescein angiography (FA) was performed to evaluated foveal avascular zone area (FAZA) and neovascularization, and optical coherence tomography (s-OCT Heidelberg Engineering), to assess retinal structure and measure macular thickness.

Results: So far, 6 eyes completed 6 month of follow-up. CRAO: n=1, CRVO: n=1 and DR: n=4. No significant changes were observed during follow-up for any measurement. Mean ± SE BCVA was 1.05 ± 0.15 at baseline and 1.10 ± 0.14 logMAR at 6 months (P = 0.3655); central macular thickness on OCT was 468.00 ± 50.89 µm at baseline and 433.29 ±65.68 µm at 6 months (P = 0.3743) and FAZA was 5.33 ± 0.84 degrees² at baseline and 5.97 ±0.98 degrees² at 6 months (P = 0.5974). No significant ocular or systemic adverse effects were observed.

Conclusions: Intravitreal CD 34+ autologous bone marrow-derived cells seems to be safe in eyes with ischemic macular edema in retinal vascular diseases, and in this small cohort was associated with no significant functional or structural retinal changes in six months. A larger number of cases and a longer follow-up are needed to confirm these findings.